2012 HIV Sourcebook for the Primary Care Provider

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3 2012 HIV Sourcebook for the Primary Care Provider Whitney Starr, MS, FNP Clinical Education Coordinator, Mountain Plains AETC Instructor, Division of Infectious Diseases, School of Medicine University of Colorado Denver Steven C. Johnson, MD Medical Director, Mountain Plains AETC Professor of Medicine, Division of Infectious Diseases, School of Medicine University of Colorado Denver Donna Sweet, MD Principal Investigator and Director, Kansas AETC Professor, Department of Internal Medicine University of Kansas School of Medicine Wichita Lucy Bradley-Springer, PhD, RN, ACRN, FAAN Principal Investigator, Mountain Plains AETC Associate Professor, Division of Infectious Diseases, School of Medicine University of Colorado Denver 3

4 The Mountain Plains Regional AIDS Education and Training Center affiliated states participating in the development and distribution of this sourcebook include Colorado, Kansas, Nebraska, New Mexico, North Dakota, South Dakota, Utah, and Wyoming. The information included in this document is intended to give an overview of HIV care for adults and adolescents and is not all-inclusive. The material is based on the DHHS guidelines available at the time of publication. The guidelines change frequently, and readers are encouraged to access updates at: To access consultation with a clinician who specializes in HIV care, contact the National HIV/AIDS Clinicians Consultation Center at: HIV Medical Consultation: (800) Post-Exposure Consultation: (888) Perinatal HIV Consultation: (888) Published 2012 Cover Photograph: Whitney Starr Design: Lucy Bradley-Springer 4

5 2012 HIV Sourcebook for the Primary Care Provider The 2012 HIV Sourcebook for the Primary Care Provider offers updated information about HIV infection for professionals who work in today s health care system. The content in this sourcebook will be useful for providers participating in various aspects of HIV care including the AIDS Education and Training Center (AETC) targeted providers (advanced practice nurses, dental professionals, nurses, pharmacists, physicians, and physician assistants), as well as other essential members of the health care team (case managers, dietitians, mental health professionals, midwives, social workers, and others). The sourcebook provides basic information about the pathophysiology of HIV infection and its modes of transmission, as well as how to recognize and diagnose HIV in the primary care setting. The basics of care for treating people living with HIV (PLWH) are included. We also address ongoing primary care issues that often arise with this patient population and are of increasing importance as HIV therapies have improved. The sourcebook is not intended to be a textbook on HIV infection, but rather a convenient reference for some of the most common issues encountered in daily practice. The recommendations herein should not be interpreted as practice guidelines or a standard of care that a clinician must follow in order to be considered competent, although the content has been derived from current testing, treatment, prophylaxis, and prevention guidelines. The authors have no authority to develop formalized approaches to the care of PLWH. As with any health care intervention, the needs of the individual patient are paramount. And, as with any chronic and difficult-to-treat condition, clinicians are encouraged to consult with and refer to specialists in the field as needed. To this end, lists of resources that can be easily accessed in local settings are provided at the end of the text. Guidelines and recommendations related to antiretroviral therapy (ART), treatment of opportunistic infections (OI), HIV testing and counseling, prevention of perinatal transmission, and post-exposure prophylaxis (PEP) are cited within this sourcebook. Reference publications may be obtained from any of the AIDS Education and Training Centers (AETCs), the Centers for Disease Control and Prevention (CDC), or at the on-line site for official federal guidelines. Complete information for accessing these resources is provided in the resource section of this sourcebook. 5

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7 2012 HIV Sourcebook for the Primary Care Provider Table of Contents page Considerations for Primary Care...1 History of HIV Infection...1 Epidemiology...1 HIV Transmission...2 Risk Assessment...3 Risk Reduction...5 Testing...5 Caring for the HIV-Infected Patient...9 Pathophysiology of HIV Infection...9 Acute HIV Infection...10 Initial Assessment Antiretroviral Therapy...13 Prophylaxis for Opportunistic Infections...18 Complications Associated with HIV Infection and ART...20 Symptom Evaluation in the HIV-Infected Patient...21 Primary Care and Disease Prevention...25 Considerations for an Aging Population...25 Immunizations...26 Cardiovascular Complications and HIV...27 Malignancies and HIV...27 Bone Loss and HIV...27 Women s Health...28 Sexually Transmitted Infections...28 Drugs and HIV...28 Mental Health Issues in the Care of the HIV-Infected Patient

8 Bibliography...31 Appendices and Resources...35 Appendix A. Occupational Post-Exposure Prophylaxis (PEP) Guidelines...37 Non-Occupational Post-Exposure Prophylaxis (npep) Guidelines...39 Appendix B. Antiretroviral Therapy...40 Appendix C. List of Abbreviations...47 Appendix D. National AIDS Services, Hotlines, and On-Line Resources...48 Appendix E. Patient Assistance Programs for HIV Medications...49 Appendix F. Regional and National AETC Programs...50 Appendix G. Mountain Plains AETC Regional Office and Local Performance Sites

9 Considerations for Primary Care The human immunodeficiency virus (HIV) epidemic presents opportunities and challenges for primary care practitioners. For many patients in the United States, HIV is a treatable chronic infection with complex and frequently changing care considerations. Like most chronic conditions, health care needs are often complicated by social, economic, and mental health conditions. Education and prevention, routine primary care, and management of co-morbidities are key factors in the continuum of care. Table 1 lists primary care activities and major responsibilities as they relate to HIV infection. Most clinicians routinely perform risk assessments as they screen patients for new or developing problems related to sexual practices or drug use. The practice of routine testing for at-risk populations allows for early identification of people infected with HIV (PLWH) and timely linkage to care. All clinicians need a basic level of understanding about HIV infection in order to enhance clinical skills, provide prevention education, and make informed decisions about care and referral. The prognosis for a person infected with HIV in the United Table 1. Primary Care Activities Related to HIV Infection Evaluate risk for HIV infection Provide education on prevention strategies Refer to risk-reduction and social service programs as needed Counsel patients about testing options Diagnose HIV infection as early as possible Evaluate stage of HIV infection at clinical presentation Encourage health-promoting behaviors Counsel patients to prevent further spread of HIV infection Assess social and emotional support and arrange referrals as needed Screen for mental health illness, past and present, particularly suicidal ideation Encourage early initiation of antiretroviral therapy (ART) Support patients in adherence to ART Provide basic primary care Provide routine health maintenance services With appropriate collaboration, consultations, and referrals: Support prescribed regimen of ART Assist in managing troublesome symptoms associated with ART diarrhea, nausea, metabolic complications, and body shape changes Monitor and recognize signs and symptoms of OIs Administer recommended prophylaxis against OIs Monitor for complications of ART Provide post-exposure prophylaxis States has improved significantly over the past decade. The average lifespan for many PLWH has neared that of the general population. Ongoing primary care including providing vaccinations, managing cardiovascular risk, identifying and treating mental illnesses, and offering general health maintenance, has become critical to the optimal health of PLWH, especially as this population lives longer and ages with HIV. Treating HIV infection may necessitate or require consultation and additional resources for many primary care providers. It is the goal of this sourcebook to present basic information necessary for primary care clinicians to evaluate risk for infection with HIV, diagnose HIV infection, and assist in the management of clinical care, as well as offer a framework for primary care activities of specific concern to PLWH. History of HIV Infection The Centers for Disease Control and Prevention (CDC) first published reports of a syndrome that led to the development of rare opportunistic infections (OIs) in The term acquired immunodeficiency syndrome (AIDS) was coined following several reports of Pneumocystis pneumonia (PCP) in previously healthy young men. These cases were seen in clusters around the United States, mostly in young men having sex with men (MSM) and on both coasts. AIDS was manifested by rare forms of infections previously seen only in those with severely suppressed immune systems, such as transplant recipients and cancer patients. Recurrences of OIs were common, and AIDS was associated with high mortality rates. Within 15 months, more than 500 cases of AIDS had been documented. Cases of AIDS were mostly found in major metropolitan areas, with the majority in Los Angeles, San Francisco, and New York City. The syndrome was soon seen not only in MSM but in other populations as well, including people with hemophilia, pregnant women, Haitian refugees, and injection drug users (IDUs). In addition to unexpected infections, several malignancies, including Kaposi s sarcoma (KS), became associated with AIDS. In 1983, HIV was recognized as the virus that caused AIDS. Epidemiology According to the United Nations Joint Programme on HIV/AIDS Report on the Global AIDS Epidemic (UNAIDS, 2010), in 2009, an estimated 33.3 million people were living with HIV, 2.6 million new cases of HIV developed, and 1.8 million HIV-related deaths occurred. The epidemic has stabilized since 2000, with decreasing death rates and fewer new infections. 1

10 Most of the epidemic burden continues to be borne by countries in Sub-Saharan Africa. The global epidemic is spread predominantly by heterosexual transmission with women making up half of all cases of HIV infection around the world. In the United States, an estimated 55,000-60,000 new cases of HIV and more than 16,000 deaths from HIVrelated conditions occur each year. The majority of PLWH in the United States continue to be MSM, although increases in women with HIV infection, especially women of color, have been noted during the past decade. Minority populations are disproportionately affected in the United States. African Americans and Hispanics/Latinos accounted for 44% and 20%, respectively, of new HIV diagnoses in During this same time, the rate of AIDS diagnoses for African American women was 15 times that of white women. Asians account for 2% of new infections and American Indians and Alaska Natives account for less than 1%. HIV Transmission HIV is primarily transmitted through exposure to infected fluids, predominantly blood, semen, vaginal secretions, and breast milk. The major means of transmission include unprotected anal and/or vaginal intercourse, sharing intravenous drug paraphernalia, and perinatally during birth HIV Transmission Mechanisms Contact with HIV-infected blood, semen, vaginal secretions, or breast milk Major means of transmission: Unprotected anal or vaginal intercourse Sharing used injection equipment Perinatal transmission or through breast milk (see Figure 1). While we know that HIV can be found in other body fluids, such as peritoneal fluid, cerebrospinal fluid, urine, saliva, sweat, and tears, no documented cases of HIV transmission have occurred after exposure to these fluids unless blood was also present. Drug Use People who use illicit drugs are at risk of acquiring HIV if they share used drug paraphernalia with infected partners. Paraphernalia include needles, syringes, cookers, and rinse water used for drug injection; pipes used to smoke drugs; and straws used to snort drugs. Hepatitis B and C viruses (HBV and HCV) are also transmitted through infected blood and sexual contact. HCV is primarily transmitted through injection drug use, but there are reports of sexual transmission of HCV in MSM. Almost one-third of PLWH are co-infected with HCV. A diagnosis of HBV or HCV is a compelling reason to also test for HIV infection. Perinatal Transmission Perinatal transmission of HIV infection can occur at any point during pregnancy, but is most likely to occur in the labor and delivery process. If the mother has not been diagnosed with HIV and/or does not receive appropriate ART during pregnancy, the risk of transmission to her infant is about 25%. The good news is that perinatal transmission rates in the United States have decreased to less than 2% or documented cases per year. Perinatal transmission decreases are directly related to (a) HIV screening for all pregnant women; (b) effective ART protocols provided to HIV-infected women during pregnancy, labor, and delivery; and (c) ART prophylaxis for perinatally exposed infants during the first 6 weeks of life. Because breast milk has been shown to contain HIV and because post-natal transmissions have occurred as a result of breastfeeding, HIV-infected mothers are counseled not to breastfeed. Sexual Transmission The most common method of HIV transmission is through unprotected sexual intercourse. Anal intercourse is the most risky sexual activity followed by vaginal intercourse. Oral sex has some risk, but is considered to be significantly less risky than unprotected anal or vaginal penetration. Genital ulcer disease, including herpes simplex virus (HSV) infection, syphilis, and chancroid, is correlated with an increased risk for acquisition of HIV infection. People who become symptomatic with a sexually transmitted infection (STI) often present for treatment, and any patient presenting with STI symptoms should be tested for HIV. CDC, 2009 HIV Incidence Data. Retrieved from incidence.htm Occupational Exposure The risk of exposure to blood and blood-borne pathogens is slightly greater for health care personnel than for people who don t work around blood. Risks in clinical settings include percutaneous injuries, such as a needle stick or a 2

11 cut with a sharp object that has been in contact with infected blood, or contact with infected blood on mucous membranes, non-intact skin, tissues, or other body fluids. Urine, feces, sweat, and saliva have not posed a risk of HIV transmission, but semen and vaginal secretions are considered potentially infectious. The risk of infection from an occupational exposure to HIV is small. A percutaneous exposure to HIV-infected blood without post-exposure prophylaxis (PEP) results in infection approximately 0.3% of the time or 1 in 300. The risk of transmission from blood or body fluid contact with a mucous membrane is estimated to be significantly lower at 0.09%. Many factors have to be considered when determining the risk of a specific occupational exposure, including the size of the device (sharp), the amount of potentially infectious fluids in the exposure, the severity of the injury to the worker, and whether the HIV status of the source patient is known. Policies from the CDC and the Occupational Safety and Health Administration require that employees be protected from exposures to infectious fluids in the work setting. Practicing Universal Precautions (including Body Substance Isolation) with the use of Personal Protective Equipment such as gloves, gowns, boots, eyewear, and masks as appropriate for patient care, decreases the risk of direct contact with blood and body fluids, thereby decreasing the risk of infection with all blood-borne pathogens. The CDC recommends PEP based on the nature and severity of exposure, the exposure source, and the available antiretroviral drugs. The availability of treatment to further decrease the risk of transmission after occupational exposure makes the reporting of all risky exposures extremely critical and increases the need for clinicians to know PEP treatment basics. As always, expert consultation should be considered as needed. For further information regarding occupational exposure and PEP, see Appendix A. Risk Assessment All health care providers regardless of clinical care setting play an important role in HIV prevention and early detection. Routine risk assessments, screening, and testing for HIV can help health care providers: identify patients who are at risk for HIV infection, provide targeted prevention education, diagnose patients who are infected with HIV, and educate PLWH about protecting their own health while decreasing the risk of transmission to others. Most cases of HIV are transmitted through sexual activity and sharing used drug paraphernalia. Many care providers find that these are difficult topics to address with their patients, but careful risk assessment is essential in the clinical care setting. Discovery of a patient s risk behaviors helps to identify areas that need to be addressed in discussions about risk reduction and the need for HIV testing. Certain behaviors are associated with a higher risk of exposure to HIV, and a careful history may provide direction for further risk assessment and targeted education and risk reduction counseling. The number of sexual partners, the sexual history of the partner(s), trading sex for money or drugs, having concurrent partners, or having sex with significantly older partners are all associated with a higher risk of HIV acquisition and transmission. The purposes of a comprehensive risk assessment are to (a) discover behaviors that can be modified to improve patient health and (b) assist with HIV diagnosis. It is critical that Table 2. History Items to Assess Risk for HIV Infection Sexual History Unprotected sexual intercourse (vaginal, anal, oral) Sexual contact with an HIVinfected person or a person at risk for HIV infection Multiple sex partners History of sexual abuse STI or related signs and symptoms Abnormal Pap smear Substance Abuse/Social History Injection drug use (IDU) Drug-using sexual partners Cocaine or methamphetamine use Sharing drug paraphernalia Alcohol dependence or detoxification Psychiatric hospitalizations Domestic violence History of incarceration Homelessness Clinical History Flu-like illness, weight loss Infections such as thrush, pneumonia, shingles, tuberculosis (TB) Hepatitis Persistent generalized lymphadenopathy (PGL) Children born to infected mothers History of transfusion or transplant Hemophilia or coagulation disorders Occupational exposure to human blood, body fluids, or tissues clinicians identify people at risk for HIV infection as early as possible because early diagnosis has been associated with: timely entry into care and treatment, better long term outcomes for the health of the individual with HIV infection, and decreased risk of HIV transmission to the individual s sex and drug-using partners 3

12 People with identified risks are more likely to be counseled about prevention measures and tested for HIV infection. Risk is best assessed by investigating health and social histories. Risk assessments provide useful information for patient care. They should be completed during the initial work up of a new patient and then implemented as a regular component of clinical care. Specific history items should relate to modes of transmission and risks associated with HIV infection, as noted in Tables 2 and 3. Conditions Associated with HIV Infection Signs and symptoms of HIV infection are frequently subtle and can be easily missed if an HIV diagnosis is not considered. For example, a young man with a persistent cough and a menopausal woman with difficult-to-treat vaginal candidiasis may each be demonstrating a manifestation of immune suppression related to HIV. Early identification of HIV infection depends on clinicians who are alert to the signs and symptoms of HIV. Common clinical conditions associated with HIV infection are listed in the final section of Table 2. This list is by no means exhaustive, but if signs and symptoms are unusual or indicate immune suppression, the clinician should consider HIV in the differential diagnosis. Risk Behaviors Major risk factors for HIV acquisition are unprotected sexual activity and sharing drug-using paraphernalia. While discussions around sexual practices and drug use can be difficult for providers and their patients, these conversations form the basis of appropriate and comprehensive health care. Inquiring about sexual behavior and drug use should be included in every comprehensive risk assessment. In addition to uncovering risk behaviors, the risk assessment can: Provide baseline information about the patient s behaviors Provide information about the patient s understanding of HIV transmission and prevention Open the door for further discussions Determine the need for prevention education Assist with testing decisions Strengthen the patient-provider relationship The value of risk assessment in the overall process of health care should not be underestimated. Table 3 provides key points for the risk assessment interview. Table 3. Key Points for the Risk Assessment Interview Risk assessments should be completed on every new patient and updated on a regular basis because circumstances and behaviors change. Arrange for a private and quiet space for the assessment. It is generally better to assess risk in a one-on-one interview between the clinician and the patient. Assure patient confidentiality and explain the importance of the risk assessment. Sexual and drug related risk assessment should be ascertained within the context of an overall risk assessment that includes questions about seat belt use, domestic violence, and other health issues. A comprehensive risk assessment related to HIV, STIs, and hepatitis should focus on: Substance use risks Sexual risk Clinical indicators of risk The following general recommendations can be applied during each part of the risk assessment: Start with less threatening topics. How often do you use alcohol or tobacco? before Do you inject drugs? and When did you start having sex? before Have you ever exchanged sex for money, drugs, or a place to sleep? Be non-judgmental. Be aware of your word choices. o Avoid pejorative words such as junkie, promiscuous, unfaithful, etc. o Labels such as gay or homosexual may not apply to individuals who have same-sex sex but who do not identify as gay. It is better to use other terms such as men who have sex with men or women who have sex with women. Don t assume anything. For example, being married does not guarantee that a person is monogamous or heterosexual and identifying as gay does not guarantee that a person has never had heterosexual sex. Use a variety of questioning techniques to gather information. Different people respond to different styles. o Direct questions about a behavior. Are you sexually active? Do you have sex with men, women, or both? Have you ever injected drugs or other substances? o Exploratory questions. How easy is it to get condoms? Do you have friends who use drugs? o Normalizing questions. Sometimes people have anal intercourse. Have you ever had anal intercourse? o Presumptive questions. Tell me about your alcohol use. How do you protect yourself from sexually transmitted diseases? Respect a patient s choice to not answer a question. This increases the chances that s/he will provide the information at a later date. I can see this is uncomfortable for you. Let s move on. At the end of the risk assessment, summarize the patient s responses to be sure he/she understood what was said. Once risks are identified, implement risk reduction interventions and screen for HIV, STIs, and hepatitis as needed. 4

13 Risk Reduction acceptable, and attainable steps. Risk reduction counseling can educate patients about ways to change risky behaviors. Risk reduction is a philosophical base that acknowledges the challenges associated with behavior change and embraces pragmatic approaches to this sometimes-difficult process. The risk reduction approach respects human value and dignity through nonjudgmental, supportive, and individually focused interventions that allow patients to make their own decisions. A central concept of risk reduction is that any movement toward healthier, safer, or less risky behavior is positive even if absolute protection is not attained. A risk reduction approach maintains that behavior change is best accomplished through a series of small, personally SAFE BEHAVIOR - no risk of HIV transmission RISK REDUCING BEHAVIOR - decrease but do not eliminate risk Table 4. Risk Reduction for Prevention of HIV Infection Sexual Transmission Drug Use Transmission Perinatal Transmission Abstain from sex. Limit sex to activities in which the penis, vagina, mouth, and/or rectum have no contact with the partner s penis, vagina, mouth, and/or rectum (outer-course). Have sex only in a mutually monogamous relationship with an uninfected partner. Use barriers consistently and correctly: Oral intercourse on male: use nonlubricated condoms. Oral intercourse on female: use dental dams, plastic wrap, or condoms that have been cut open. Vaginal intercourse: use male or female condoms. Anal intercourse: use male condoms or female condoms with inner ring removed. Engage in care for HIV infection: Establish and adhere to effective ART regimen to lower viral load Don t use drugs. Don t inject drugs: if drugs are used, smoke, snort, swallow, or apply to oral or rectal mucosa instead. Use only clean equipment that has not been used by anyone else. This includes needles, cookers, pipes, straws, etc. Clean used injecting equipment before use: Rinse used needle and syringe with tap water. Fill syringe and needle with fullstrength bleach, shake for 30 seconds, squirt bleach out; repeat twice. Rinse twice with tap water. Do not reuse or share bleach or rinse water. Engage in care for HIV infection: Establish and adhere to effective ART regimen to lower viral load Clinicians begin to implement risk reduction by helping patients assess and acknowledge individual risk. Responses are then used to discuss healthier, safer, and less risky behaviors that are acceptable to the patient. This tactic provides a spectrum of choices while reaffirming the patient s control over personal life events. Table 4 reviews sexual- and drug-related HIV prevention measures from a risk reduction perspective, creating a continuum from safe (behaviors that eliminate risk) to risk reducing (behaviors that decrease, but do not eliminate, risk). Clinicians should provide education and referrals specific to the patient s chosen risk-reducing behaviors and Prevent HIV in women. In HIV-infected women: Use birth control to prevent pregnancy. Terminate pregnancy. Plan pregnancy when mother s viral load is low and the CD4+ T cell count is relatively high. Treat HIV-infected mother with appropriate ART during pregnancy, labor, and delivery; consider elective Cesarean section, especially if viral load is detectable; treat newborn after birth (see DHHS treatment guidelines for pregnancy). goals. For example, it does little good to discuss complete cessation of substance use with a patient who is not ready to quit using drugs. In this situation, offering strategies to use drugs in a safer manner (e.g., accessing sterile syringes and needles or changing from injecting to smoking the drug of choice) or less often may be more helpful. And, because transmission from HIV-infected drug users to their sexual partners is a common route of infection, all counseling to drug users should include information about safer sexual practices. Testing Approximately one in five persons with HIV infection in the United States is unaware of being infected and, unfortunately, many patients are still diagnosed late in the course of the disease; indeed, many who are newly diagnosed with HIV progress to AIDS within 1 year. Early detection of HIV infection is important: it allows infected people to enter into treatment and helps to reduce the risk of HIV transmission and new infections. In 2006, the CDC published revised recommendations for HIV testing, with the goal of increasing the number of people 5

14 who were aware of their HIV status. Please note that when state laws and individual facility policies and procedures on HIV testing do not match current CDC recommendations, state and individual facility regulations take precedence. The CDC recommends that voluntary opt-out testing be part of routine clinical care in all health care settings and for all patients, regardless of the individual s risk factors. Screening should be offered to all individuals ages 13-64, and especially to patients in treatment for TB, patients in care for STIs, women considering contraception or pregnancy, pregnant women, and women who present in labor with no documented HIV test. Health care providers should inform each patient about the recommendation to test all patients for HIV. Opt-out testing is recommended. In opt-out testing, the patient is informed, either in a verbal discussion or in writing, that the test will be performed unless the patient declines. Opportunity should be provided for discussion as requested by the patient. A separate consent form for HIV testing is not recommended; the general consent for medical care is sufficient. For those individuals at high risk for acquiring HIV, testing is recommended on at least an annual basis. Individuals at high risk for aquiring HIV include IDUs and their sex partners, people who have sex with more than one partner or whose sex partner has sex with more than one partner, people who exchange sex for drugs or money, and sex partners of individuals known to have HIV. Universal screening has been routinely implemented for all blood donors, and has almost completely eliminated the risk of acquiring HIV through transfusions. Likewise, testing for HIV infection has become the standard of care for pregnant women, allowing these women to make informed decisions about clinical care and dramatically reducing the rate of perinatal transmission. Systems need to be in place HIV Infection at testing centers to provide appropriate follow-up care by linking newly diagnosed and high-risk individuals to treatment and prevention services. Linking individuals to care early in the course of the disease is beneficial for the health of the individual as well as for the health of the community. The majority of PLWH change their risk behavior profiles after they become aware of being infected, and this behavior change can lead to a dramatic reduction in new infections. Testing Methods Figure 2. HIV Testing Protocol HIV-1/HIV-2 Antibody Test by ELISA Positive Confirm w/ Western Blot or IFA Positive Negative The most common screening methods for HIV infection use an enzyme immunoassay (EIA or ELISA), a highly sensitive, low-cost test that screens for HIV antibodies. Testing is considered to be either rapid (on site) or conventional (sent to a reference lab). Figure 2 shows a graphic depiction of the testing process. Rapid HIV tests use whole blood, plasma, or oral fluid to detect antibodies. Specimens are analyzed in an officebased lab with appropriate CLIA waiver. Test results are usually available within 20 minutes. Because patients do not have to return to clinic on another day to receive results, rapid testing increases the number of people who receive results. They also increase opportunities for timely access to counseling and treatment services. Rapid tests are especially helpful in time-sensitive situations, such as a case of occupational exposure or a woman presenting in labor with an unknown HIV status. Although rapid results are accurate enough to provide immediate, preliminary results to the patient, positive results should be confirmed with a more specific test, such as a Western Blot or immunoflourescence assay (IFA). This will require a blood sample and off-site laboratory analysis. Negative Indeterminate If concerned about acute HIV infection, consider HIV RNA testing. With recent risk exposure, retest with HIV ELISA up to 6 months after exposure Retest for HIV antibody or HIV RNA; consider risk factors for HIV-2 Conventional EIA tests (non- rapid) can be done on oral fluid, blood, or urine. Results may not be available for several days to weeks, depending on the reference lab used. If the EIA is positive for HIV antibody, it should also be confirmed by a more specific test, such as the Western Blot or IFA, before concluding that the patient is infected with HIV. The lab will generally complete this step on the original specimen before reporting back to the provider who ordered the test. If Western Blot or IFA results are negative or indeterminate, it is recommended that the test be repeated 4 weeks after the initial test or, if there is high risk for HIV infection, to immediately test for HIV RNA, which will diagnose HIV based on viremia. RNA tests are expensive and should only be used after indeterminate screening test results in the context of likely infection. An HIV screening test that detects both antibodies and p24 antigen, a protein from the virus, has been recently licensed. It is known as the 4th generation HIV assay, and it has the 6

15 potential to enhance the sensitivity of screening for patients who are in the earliest stages of HIV infection. Appropriate recommendations for further testing and risk prevention depend on an understanding of the testing window period and the patient s risk history. Rapid and conventional screening tests for HIV detect antibodies rather than actual virus (antigen) and may, therefore, not detect a recent infection. It takes 2-12 weeks after infection for the individual s immune system to produce enough antibodies to register a positive test result. During the window period, a negative test does not rule out HIV infection. In fact, recently infected people usually have high levels of viremia, and are at greater risk of infecting others even while testing negative for HIV. People who have had a potential for or an actual exposure to HIV should be encouraged to take precautions to decrease the risk of HIV transmission during the window period. A negative test in a person with a recent exposure or continuing risk should, therefore, have a repeat test in a few weeks. In settings where recent infection is a significant concern, diagnostic testing for acute HIV infection via plasma RNA testing should be ordered. The window period is the time between infection with HIV and having enough HIV antibodies to be detected through testing. Communicating test results. According to the 2006 CDC recommendations for HIV testing, all patients should be provided with oral or written information about HIV testing, the meaning of positive and negative test results, how results will be communicated, and an opportunity to ask questions. The CDC recommends testing without risk assessment and prevention counseling, especially in busy clinical settings where time is a barrier to testing. However, testing may provide an opportunity for discussions about HIV, transmission, risk, and prevention. If the patient refuses the test, this should be documented in the medical record, and testing should be offered at the next clinic appointment. Test results should be discussed in private to insure patient confidentiality. Post-test counseling is recommended for every positive result and should take place when results are delivered. A positive test result can be difficult to disclose and clinicians should be prepared for an emotional response from the patient. Some patients become understandably distressed about a positive test and it is appropriate to assess support systems (e.g., friends, family, access to mental health services) and to make referrals as needed. Post-test counseling should be individualized to the patient, but needs to include the following: Remind the patient that HIV infection, while not curable, is treatable and that many people remain well for prolonged periods of time. Discuss ways to limit transmission of the disease to others. Discuss ways to avoid exposure to other infectious diseases, including TB, hepatitis, and STIs. Review safer sexual and drug use practices. Encourage patients to disclose to high-risk contacts who may also need to be tested. Offer anonymous/ alternate methods for disclosure, especially when the patient feels there are dangers with disclosure. Set up a return appointment within 1 to 3 weeks to initiate care, continue education, and, if possible, be connected with a specialist. When negative test results are delivered, the risk for false negative results, based on the window period and assessed risk for the individual, should be discussed. High-risk behavior anytime during the previous 6 months will indicate the need for another HIV test in 4 weeks to 3 months. Reinforcing ways to reduce risk behaviors is also appropriate. Suicide assessment. It is important to determine the suicide risk of an individual newly diagnosed with HIV and throughout the course of care, as the rate of suicide is three times higher in PLWH than the general population. A pre-existing psychiatric illness increases an individual s risk for suicide. It is important to screen for depression and suicidal ideation when disclosing positive test results and when establishing care. Previous suicide attempts are strong predictors of future behaviors, especially during times of extreme stress. Certain situations are associated with high stress in HIV, including the time of initial diagnosis and with signs or symptoms of advancing disease. Biological and social factors (e.g., state of health, social support) should be assessed when determining the suicide risk of someone newly diagnosed with HIV. Alcohol often plays a role in suicide attempts, and has been documented as a factor in up to 50% of all cases. The first step in suicide prevention is to initiate a dialogue about the patient s mental wellbeing. Asking a patient about tendencies or thoughts of suicide does not increase the risk that someone will attempt suicide and is part of providing comprehensive care. Referrals are appropriate when a patient is suicidal, has faced previous challenges with mental health problems, would like support related to mental health concerns, or needs additional assistance adjusting to a diagnosis of HIV infection. 7

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17 Caring for the HIV-Infected Patient An understanding of the pathophysiology of HIV is important when caring for patients with HIV infection. Knowing about the HIV replication process can help providers and patients understand the basic principles of treatment and prevention. Pathophysiology of HIV Infection As with all viruses, HIV is an obligate parasite: It cannot survive and replicate unless it is inside a living cell. HIV is an RNA virus and it is one of several retroviruses that can cause human disease. Retroviruses replicate by using an RNA template to create a DNA strand. Each virion contains two copies of HIV RNA, enzymes and other proteins needed for replication, and a viral capsid. The enzymes, including reverse transcriptase, integrase, and protease, are the targets for many licensed antiretroviral agents. A phospholipid bilayer membrane with protein complexes embedded in the membrane surrounds the viral capsid. These protein complexes allow the membrane to fuse or bind to specific receptor sites on cells, including the CD4 receptor and co-receptor sites on CD4+ T lymphocytes. This binding enables the virus to insert genetic material and enzymes into the cell. Once inside the cell, viral RNA is transcribed into proviral DNA with the assistance of reverse transcriptase. The proviral DNA is then integrated into the most active regions of the genetic material of the cell with the help of the enzyme integrase. The proviral Figure 3. Natural Progression of HIV Infection Without intervention, viral load will continue to increase as CD4+T cell counts decline. Acute infection* Days/Weeks Years CD4+ T Cells HIV Viral Load (HIV RNA) *Acute HIV infection often manifests as a mononucleosis-like illness. During this stage, the patient will test negative until sufficient HIV antibodies have been produced. DNA in the genome then directs viral replication in the cell. Activation of the cell produces a long strand of viral RNA that migrates into the cytoplasm of the cell. These long strands are cleaved into smaller, viable strands with the assistance of the enzyme protease. New virions containing RNA and essential enzymes can then be assembled. New virions bud from the host cell, taking a piece of the cell s membrane to form the new viral envelope. Although HIV can infect several types of human cells, immune dysfunction results predominantly from the destruction of helper T cells, more appropriately called CD4+ T lymphocytes (or CD4+ T cells). These cells play a pivotal role in the human immune response by (a) recognizing infectious and neoplastic processes and (b) secreting cytokines that initiate the body s defense mechanisms. CD4+ T cells are targeted by HIV because they have more CD4 receptor sites on their surfaces than other cells. The number of CD4+ T cells is the primary marker for immune function in HIV and is the main determinant of risk for developing opportunistic disease. Opportunistic diseases rarely occur early in the course of HIV disease when the CD4+ T cell count is near normal at 500 cells/mm³. As the disease progresses and the number of CD4+ T cells falls, the risk of opportunistic disease increases. Furthermore, when the CD4+ T cell count falls below 200 cells/mm³, the patient is considered to have a diagnosis of AIDS. HIV is a dynamic disease, with billions of virions produced daily. During the first few weeks after infection, the virus replicates rapidly, producing a high level of viremia in the peripheral blood and other body fluids including vaginal secretions and semen. During this initial phase, persons infected with HIV are extremely infectious to others. Initial (or acute) infection is associated with a significant drop in CD4+ T cells and an increased viral load. An immune response is triggered, leading to rapid CD4+ T cell replacement and HIV-specific antibody production. Most HIV screening tests detect the presence of these antibodies, which can take several days to weeks to develop. The viral load drops as the immune response is established. (See Figure 3.) HIV infection is typically a slowly progressing illness. The effects of the virus are often not seen for several years even in the absence of treatment. However, HIV is quick to establish a persistent infection in reservoirs, mostly in lymphatic tissues. HIV infection will usually progress over several years, although virulence of the strain of virus as well as individual host factors may vary the course of disease. On average, untreated HIV infection will lead to severe immune suppression and death in 8-12 years. Clinical manifestations depend on the stage of infection and the extent of immune dysfunction. 9

18 AIDS is a specific diagnosis that indicates progressive or advanced disease. The 1993 AIDS surveillance case definition is still used; it includes all PLWH with (a) < 200 CD4+ T cells/mm³, or (b) a CD4+ T cell proportion (CD4%) < 14% of total lymphocytes, or (c) one of the other AIDS-defining conditions listed in Table 5. Acute HIV Infection Acute HIV infection, also known as acute retroviral syndrome, primary HIV infection, or acute seroconversion illness, refers to a syndrome experienced by many individuals when they become infected with HIV. During acute infection, symptoms can range from mild to severe. Patients may experience fever, headache, diffuse lymphadenopathy, arthralgia, diarrhea, pharyngitis, or rash (see Table 6). This mononucleosis-like illness usually occurs 2-12 weeks after exposure to HIV and symptoms can last 2-3 weeks or longer. Some patients also experience meningitis or encephalitis. The onset of symptoms has been shown to coincide with peak viremia. Unfortunately, patients and providers often mistakenly attribute acute infection and its associated symptoms to a transient viral infection such as the flu. As a result, few people with HIV are diagnosed during acute infection. Acute HIV infection should be included in the differential diagnosis for all at-risk patients who present with a flu- or mononucleosis-like illness or with unexplained aseptic meningitis. See Tables 2 and 3 for information on patients at risk for HIV and areas of key interest in a risk assessment for HIV. Diagnosis during acute HIV infection can be important to the individual s health. During the first few days to weeks of infection, HIV establishes reservoirs, first in the local tissues of the host exposure site, and then in lymphatic tissues through systemic circulation. Treating HIV early in the infectious process could limit the Table 5. Conditions in the 1993 AIDS Surveillance Case Definition CD4+T cell count of < 200 Lymphoma, immunoblastic (or cell/mm 3 or percentage < 14% equivalent term) Candidiasis of esophagus, bronchi, Lymphoma, primary in brain trachea, or lungs Mycobacterium avium complex Cervical cancer, invasive (MAC), or M. kansasii, Coccidioidomycosis, disseminated disseminated or extrapulmonary or extrapulmonary Mycobacterium tuberculosis Cryptococcosis, extrapulmonary (MTB/TB), any site (pulmonary or Cryptosporidiosis, chronic extrapulmonary) intestinal (> 1 month duration) Mycobacterium, other species or Cytomegalovirus (CMV) disease unidentified species disseminated (other than liver, spleen, or nodes) or extrapulmonary CMV retinitis (with loss of vision) Pneumocystis jiroveci (formerly HIV encephalopathy known as P. carinii) pneumonia HSV: chronic ulcers (> 1 month (PCP) duration); or bronchitis, Pneumonia, recurrent bacterial ( pneumonitis, or esophagitis 2 episodes in 12 months) Histoplasmosis, disseminated or Progressive multifocal extrapulmonary leukoencephalopathy (PML) Isosporiasis, chronic intestinal (>1 Salmonella septicemia, recurrent month duration) Toxoplasmosis of brain KS Wasting syndrome due to HIV Lymphoma, Burkitt's (or equivalent term) Table 6: Signs and Symptoms of Acute HIV-1 Infection Signs and Symptoms % of Patients Fever > Fatigue > Rash > Pharyngitis Myalgia or arthralgia Lymphadenopathy Headache Night sweats 50 Thrombocytopenia 45 Leukopenia 40 Aseptic meningitis 24 Elevated hepatic liver enzymes 21 Oral ulcers Genital ulcers 5-15 Adapted from: Kahn, J.O., & Walker, B.D. (1998). Acute human immunodeficiency virus type 1 infection. NEJM, 339(1), ability of the virus to establish reservoirs in these distant sites. If diagnosed during this phase, the patient should be considered for immediate treatment and referral to or consultation with an HIV-expert provider is encouraged to assure cutting-edge, evidence-based treatment. Diagnosis during the acute stage of infection is also important for the public health. Individuals with acute HIV infection typically have high levels of HIV in their blood (often > 1,000,000 copies/ml). During this stage, blood, semen, and vaginal secretions are highly infectious. Identification of patients with acute HIV infection provides an opportunity for early counseling and prevention education, which have the potential to reduce risky behaviors and prevent HIV transmission to others. Tests used to diagnose individuals with acute HIV infection include the HIV antibody test and the HIV viral load (HIV PCR) assay (see Part 1). During acute infection, the antibody test is usually negative because the patient is in the window period. A patient who tests negative on initial screening with an ELISA test (see Figure 2) and presents a history of high risk behaviors and/or symptoms of acute infection, should be offered an HIV viral load test. If diagnostic testing is initiated, it is important to have contact information for the patient and to schedule an appointment to discuss the test results, which may not be available for several days. Counsel patients that they may be highly infectious and 10

19 that, until results are known, they should minimize the risk of transmission to others. Recommendations will vary from patient to patient, but patients who are sexually active should abstain from sex or use condoms and patients who use drugs should not share drug-using equipment with others. The clinician who orders the test must be able to initiate counseling or to refer the patient to an easily accessible professional colleague who can provide counseling and education. Initial Assessment An individualized treatment plan for a patient with HIV infection is based on medical history, physical exam, and laboratory analysis. Baseline assessments provide information that will help to determine treatment options. As with any patient, health care maintenance is an important aspect of ongoing care. History Medical history. A comprehensive medical history should be completed at the initial visit. A focused history of the patient s HIV infection (including identification of risk factors, date of positive HIV test, history of negative HIV tests, history of signs and symptoms of acute HIV infection, history of treatment with ART, adverse effects of ART, and any history of OIs or other infections, including HBV infection and HCV infection) is needed. For patients with a history of HIV treatment, information about previous CD4+ T cell counts and viral loads is useful. A focused review of symptoms is important at every visit to elicit signs and symptoms of HIV infection or OIs. Acute and chronic health conditions need to be identified and a family medical history should be obtained as well. Table 7 lists some important questions to ask during the medical history. Social history. A thorough social history, including housing, finances, employment, and social support, should be obtained. These factors may affect the patient s ability to access care and to adhere to treatment. Substance Use History. Substance use and Table 7. Initial History After HIV Diagnosis History of previous HIV testing and test results Past exposure to related infections Hepatitis Other STIs TB Other potentially chronic infections such as histoplasmosis, coccidiodomycosis History of recurrent infections such as pneumonia, vaginal candidiasis History of present illness, including: Weight loss, fever, chills, night sweats Changes in mentation Headaches Changes in vision Pain in mouth, pharynx Difficulty swallowing Shortness of breath, cough, chest discomfort Diarrhea, nausea, vomiting Numbness, tingling, weakness in extremities Changes in skin/rash Vaginal or urethral discharge, lesions, or dysuria Rectal/anal lesions or bleeding dependence on tobacco, alcohol, and other recreational drugs should be evaluated as well. Addictions can have serious consequences on the physical and social wellbeing of patients that can ultimately affect outcomes of treatment. Patients with active substance abuse issues should be referred to treatment. Sexual history. A careful sexual history should elicit information about past and current sexual practices, protection from STIs, preferred method of contraception, current STIs, and the history and treatment of previous STIs. Patients with a diagnosis of HIV infection may have taken considerable sexual risks that have affected their physical and emotional health. Family history. A family medical history can help to establish an appropriate primary care screening program for those infected with HIV. Questions should elicit information regarding risks for early development of malignancies, cardiovascular disease, and atherosclerotic disease. A history of myocardial infarction in a first-degree male relative before the age of 55 and before the age of 65 in a female relative helps to determine cardiovascular risk factors. Physical Examination A complete physical examination is required for all patients with a diagnosis of HIV infection, even if no symptoms are present. Immunodeficiency may allow infections to become established without early symptoms. Careful inspection of the oral cavity, skin, and lymph nodes is especially important. Table 8 lists important physical findings in PLWH, along with their potential causes. Because HIV is a chronic disease, it is also necessary to continue all age-appropriate screening exams. Laboratory Tests Of the many laboratory tests used to support diagnosis and therapy in HIV infection (see Table 9), two are critical: the HIV viral load assay and the CD4+ T cell count. The combination of HIV viral load and CD4+ T cell testing provides the best information for initiating, monitoring, and changing ART. The HIV viral load indicates the level of virus circulating in the blood and the ability of the virus to multiply. The CD4+ T cell count measures the ability of the immune system to protect the body from infections. For both tests, it is important to use the same laboratory test over time and, if possible, to avoid testing on days when the patient is acutely ill. 11

20 Table 8. Physical Examination of the HIV-Infected Person System Physical Signs Potential Etiology General Skin Oral Mucosa Eyes Chest Anogenital Nodes CNS Weight loss, cachexia, fever, chills, fatigue, night sweats Pigmented lesions of recent onset, ulceration, erythema, exfoliation Whitish plaques, ulceration, poor dentition, pigmented lesions Diminished peripheral vision, retinitis, changes in visual acuity, funduscopic abnormalities Cough, fine rales, tachypnea, cyanosis, hemoptysis, abnormal chest x-ray Ulceration, fissures, discharge, lesions Enlargement, especially noninguinal Dementia, focal deficits, meningitis HIV infection, OI, or malignancy KS, HSV infection, varicella zoster virus (VZV) infection, impetigo, seborrheic dermatitis, folliculitis, xeroderma candidiasis, HSV, KS, oral hairy leukoplakia (OHL), gingivitis CMV retinitis, syphilis, HSV retinitis/uveitis, VZV retinitis, syphilis, HIV retinopathy bacterial, viral, atypical, or fungal pneumonia; PCP; TB; pulmonary KS; CMV pneumonitis Candidiasis, syphilitic chancre, HSV infection, human papillomavirus (HPV) infection MAC, lymphoma, TB, HIV infection PML, toxoplasmosis, lymphoma, syphilis, cryptococcosis HIV viral load testing (HIV RNA Assay). Viral replication in HIV infection is rapid and continuous. From the time of infection, billions of new viral copies are produced daily. HIV viral load is a quantitative measure of HIV viral RNA in the plasma. A stable level or set point occurs after primary infection and remains relatively constant in the absence of disease progression, therapeutic effect, and/or disease exacerbation. Plasma HIV RNA quantitation is the best determinant of treatment efficacy, and is also related to the level of infectivity. Several different assays are currently available to measure plasma HIV RNA. While correlation between plasma HIV RNA levels is high between methods, each is a distinct technique with different reference standards. Each technique has a different definition of undetectable, none of which indicate a total absence or clearance of virus. Providers should become familiar with the assay most frequently used in their laboratories. CD4+ T cell count. The CD4+ T lymphocyte count is the best marker for the immune deficiency associated with HIV infection. The absolute CD4+ T cell count reflects the number of CD4+ T cells/mm³; the percentage of CD4+ T cells is a subset of all lymphocytes (CD4%). Depending on the laboratory, the normal reference range for an adult CD4+ T cell count absent of disease would be about cells/mm³. The normal range for CD4% will vary depending on the lab, but > 29% corresponds with a CD4+ T cell count > 500 cells/mm³ and < 14% (which qualifies as an AIDS diagnosis) corresponds with a CD4+ T cell count < 200 cells/mm³. The absolute CD4+ T cell count can vary in the same individual depending on the time of day the blood is drawn, the laboratory used, the presence of acute illness, or other factors. Concomitant medication, such as corticosteroids or interferon, can also lower the CD4+ T cell count. Table 9. Initial Laboratory Evaluation of the HIV-Infected Person The Basics CBC with differential Platelet count Chemistry profile (with LFTs, BUN, and creatinine) PPD test or IGRA Cervical pap smear Lipid profile and blood glucose Chlamydia and gonorrhea testing as appropriate Urinalysis HIV Specific Tests CD4+ T cell count (absolute and percentage) HIV viral load (HIV plasma RNA) HIV resistance testing (genotype at baseline and change of therapies, phenotype in treatmentexperienced patients prior to changing therapy) Screening for Hepatitis Co-infection Hepatitis A: Hep A Ab Hepatitis B: HBsAb, HBsAg, HBcAb Hepatitis C: Hep C Ab Screening for OIs & Other Infections PPD or IGRA AFB blood cultures* Screening for STIs Syphilis serology** Toxoplasma serology G6PD*** Other Testing to Guide ART Tropism assay (only if use of maraviroc is being considered) HLA-B*5701 testing (if use of abacavir is being considered) *Consider testing for MAC if CD4+ T cell count < 50 cells/mm 3 ** Baseline syphilis testing is important in areas of high prevalence. If positive, consult expert guidelines regarding treatment and CSF examination if indicated. ***Consider testing in high-risk populations, including Mediterranean or African descent 12

21 HIV resistance testing. Resistance to antiretroviral medications is a major clinical concern. Resistance leads to treatment failure and the risk of transmitting drug-resistant virus. Resistance testing is used to determine the presence of a drug-resistant strain of HIV in order to prevent the use of medications likely to be ineffective. Two types of laboratory assays are available to help determine resistance: (a) genotypic resistance testing identifies mutations in the genetic code of HIV that are associated with drug resistance and (b) phenotypic resistance testing determines if the patient s HIV can replicate in the presence of specific antiretroviral agents (similar to antibiotic sensitivity testing). Baseline resistance testing with a genotype is recommended before the initiation of ART and is ideally performed during the patient s initial visit. If ART is deferred, genotypic resistance testing should be repeated prior to starting therapy. Additional Laboratory Evaluation. Laboratory tests should be used to identify HIV-related complications or co-infections (syphilis serology; tuberculin skin test or interferon gamma release assay [IGRA]; gynecologic exam with Pap smear; hepatitis A, B, and C virus serology; and toxoplasmosis IgG serology). Baseline metabolic parameters, including a fasting lipid panel should also be obtained. Other tests should be performed as clinically indicated (e.g. chest x-ray, ophthalmologic exam). Prior to initiating a regimen containing abacavir, a patient should be screened for HLA-B*5701. This mutation is associated with a hypersensitivity reaction to abacavir; any patient who is HLA-B*5701 positive should, therefore, not receive abacavir and should have abacavir listed as a drug allergy. A tropism assay is also needed prior to starting therapy with the CCR5 antagonist, maraviroc, as this medication is only effective if the patient has a CCR5-using HIV strain. 100% 80% 60% 40% 20% Figure 4. Proportion of HIV-Infected Individuals in the United States at Each Stage of Care 100% 1,178,350 80% 941,950 62% 725,302 41% 36% 28% , ,475 Antiretroviral Therapy Treatment options for HIV infection have advanced rapidly since Today s ART has fewer side effects than older regimens. In addition, the dosing of ART has been simplified to either once or twice daily regimens, and the majority of patients are able to successfully tolerate and adhere to their ART regimens. PLWH with a comprehensive treatment plan can live for many years and most have the potential to live normal life spans. Despite advances in treatment, of the 1.1 million PLWH in the United States, only 28% are in consistent care, on an ART regimen, and have a suppressed viral load (see Figure 4). These data imply that the existence of effective combination ART is necessary, but not sufficient, for treatment success. Other requirements for success include access to care, retention in long-term care, consistent access to ART, and the ability to adhere to the treatment protocol. ART has been shown to slow disease progression and to improve survival and quality of life for PLWH. The goal of ART is to decrease viral replication for as long as possible, thus reducing the chance of viral mutations and drug resistance. Combination drug regimens have proven effective in dramatically reducing the quantity of circulating virus in the blood, often to levels below detection by most lab assays. It is important to note, however, that not all patients can tolerate or adhere to combination therapies, and 10-20% or more of patients will not be able to achieve the goal of an undetectable viral load. It is also important to remember that an undetectable viral load does not mean the virus has been eliminated nor that the patient is cured. Below the level of detection indicates that the viral load in a peripheral blood sample is too low to be detected with current tests. It does not reveal the level of HIV that remains in the tissues. The initiation of ART should be based on the patient s clinical presentation, potential for disease progression, treatment history, desire to start lifelong therapy, and understanding of adherence parameters. See Table 10 for a list of the benefits and risks of early initiation of ART. 0% infected diagnosed care care viral load <200 copies/ml Source: CDC 13

22 Table 10. Benefits and Risks of Early HIV Treatment Potential Benefits Maintain higher CD4+ T cell count and prevent potentially irreversible damage to the immune system Decrease risk for HIV-associated complications that occur more often at CD4+ T cell count > 350 cells/mm (TB, certain malignancies, and HIV-associated cognitive impairment) Decrease risk of non-opportunistic complications, including CVD, renal disease, liver disease, malignancies, and infections Decrease risk of HIV transmission to others Potential Risks Treatment-related side effects and toxicities Drug resistance with incomplete viral suppression, resulting in loss of future options for therapy Increase total time on medication with greater chance of treatment fatigue Transmission of drug-resistant virus by patients who do not maintain full virologic suppression Antiretroviral Recommendations With the advent of combination treatment regimens, ART has become quite complex. A panel of experts periodically publishes revised principles and recommendations for treatment of HIV infection. The Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents recommend that clinicians with limited HIV care experience seek the consultation of clinicians with more experience in this complex and rapidly evolving field. Most primary care clinicians use consultation services for other complex disease processes and this is a critical component of HIV care. Specific guidelines (Public Health Service Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States) are also available for using ART in pregnant women and for prevention of perinatal transmission. Refer to the guidelines for concerns and specific issues regarding the use of ART in patients with drug resistance or in specific populations including adolescents; IDUs; patients who are co-infected with hepatitis B, hepatitis C, or TB; and women of child-bearing age. Complete principles and guidelines are available from the AETCs and other resources (see resources section). Federal HIV Guidelines can be accessed at Initiating ART: Acute HIV Infection Clinicians and patients should be aware that therapy for acute HIV infection is based on theoretical benefits and is, therefore, optional. Potential benefits and risks of treating acute HIV infection should be considered prior to initiating therapy (see Table 11). If the clinician and patient choose to treat acute HIV infection, resistance testing prior to treatment is recommended. The goal of therapy should be to suppress plasma HIV RNA levels to below detectable levels. Routine testing for plasma HIV RNA levels, CD4+ T cell counts, and toxicity screening should be performed as with other patients on ART. As with all ART regimens, consultation with an HIV-experienced clinician is recommended. Initiating ART: The Chronically HIV-Infected Patient Starting or changing therapy should be based on clinical status, HIV viral load assays, HIV resistance testing, CD4+ T cell counts, and individual patient issues. Viral load tests should be performed within the first 2-8 weeks of therapy to assess effectiveness. Table 11. Potential Benefits and Risks of Treating Acute HIV Infection Potential Benefits Reduce viral replication Reduce symptoms of acute HIV infection Alter viral set point, affecting progression Reduce rate of viral mutations Reduce risk of viral transmission Reduce immunologic damage Potential Risks Drug toxicities Drug resistance Need for continuous therapy Adverse effect on quality of life Adapted from: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available at Nearly all individuals with HIV infection are candidates for treatment, if desired by the patient. Current guidelines for initiating ART are outlined in Table 12. Early treatment may be considered based on the patient s individual risk for immunologic decline, disease progression, and motivation to begin therapy. Decisions regarding the initiation of ART must be individualized to the patient after appropriate patient education regarding disease stage, drug side effects, long-term toxicity, co-morbidities, and adherence issues. Regardless of CD4+ T cell count, current guidelines also recommend ART be initiated in several conditions including: pregnancy, an AIDS-defining condition, chronic co-infection of HBV or HCV, and if there are signs of HIV-associated nepropathy. ART is also used to limit transmission in serodiscordant couples. 14

23 Table 12. Indications for Initiation of Antiretroviral Therapy for HIV-1 Infection This table provides general guidance rather than absolute recommendations for an individual patient. Before initiating therapy, patient counseling and education should be provided with a focus on the benefits and risks of therapy, adverse effects, and adherence. Clinical Conditions Recommendations All HIV-infected individuals* History of AIDS-defining illness** Pregnant women*** Persons with HIV-associated nephropathy Persons co-infected with hepatitis B virus (HBV), when HBV treatment is indicated (Treatment with fully suppressive antiviral drugs active against both HIV and HBV is recommended.) ART should be initiated. *Treatment is recommended for all HIV-infected individuals. All decisions regarding initiation of antiretroviral therapy should include evaluation of immune suppression as determined by the CD4+T cell count and clinical presentation, the potential benefits and risks of starting treatment, and the willingness of the patient to commit to lifelong antiretroviral therapy. **AIDS-defining illness per CDC, 1993 ***For women who do not require ART for their own health, consideration can be given to discontinuing antiretroviral drugs postpartum. For more informatioin, please refer to the Public Health Service Reccomendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women and Interventions to Reduce Perinatal HIV-1 Transmission in the United States. Table adapted from Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents; DHHS March 27, 2012, available at Inflammatory Response Treatment of patients with ART who have an underlying, recognized or unrecognized OI, can occasionally elicit an inflammatory response. This syndrome, often referred to as immune reconstitution syndrome or immune reconstitution inflammatory syndrome (IRIS), presents with a fever and worsening of OI symptoms weeks after starting ART. Use of non-steroidal anti-inflammatory drugs (NSAIDS) or corticosteroids can help alleviate this inflammatory reaction. Medication Adherence Adherence to treatment regimens is an important therapeutic concern. Incomplete adherence can lead to treatment failure, drug resistance, and the risk for transmission of drug-resistant virus, making this a critical topic for patient education. Patient readiness is key to medication adherence, and it is important to allow the patient time to make the decision to initiate therapy. Treatment regimens have become much easier in recent years (once- or twice-a-day dosing, fewer pills, fewer side effects), but adherence to what will be a life-long course of therapy is still difficult for many patients. Medication adherence can be a challenge for even the most motivated patients. While 100% adherence is optimal, missed doses should be an expected part of treatment. Clinical studies indicate that best results are achieved with adherence rates of > 95%. PLWH who choose to initiate ART will need continuous support to maintain therapy. Judgmental and punitive approaches to less-than-optimal adherence should be avoided, as they are likely to decrease the patient s willingness to share accurate information with the clinician. Table 13 lists some factors to consider when addressing adherence concerns with a patient. Adherence interventions should be individualized and consistent with the current treatment guidelines. Currently Available Antiretroviral Drugs Many antiretroviral agents are now approved for use in the United States, with more in development. Antiretroviral drugs fall into 6 classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors, and two types of entry inhibitors: fusion inhibitors and CCR5 antagonists (see Appendix B). 15

24 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI/NtRTIs)work at an early stage in viral replication. They block reverse transcriptase, an enzyme required for the virus to multiply, by mimicking nucleosides or nucleotides in the growing DNA chain. Once the DNA chain is terminated, the individual virus can no longer replicate, and damage to the immune system is slowed. NRTIs are the cornerstone of combination therapy. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) also block reverse transcriptase. Resistance develops quickly to NNRTIs when used alone, making it extremely important that they be used in maximally suppressive combination therapies. NNRTIs are often used in combination with NRTIs. Protease Inhibitors (PIs) work against HIV in a late stage of the viral replication process by interfering with the protease enzyme s ability to make new copies of HIV, thus producing viruses that are incapable of infecting new cells. The PIs, when used in combination with other antiretroviral agents, offer potent anti-hiv activity. Entry Inhibitors prevent HIV entry into the target cell through a variety of mechanisms. Enfuvirtide (T20), a fusion inhibitor, interferes with the process of viral binding (fusion) to the cell membrane by binding to proteins on the surface of the cell, which then prevents the virus from binding to the target cell. Maraviroc (MVC) prevents entry by blocking CCR5, a co-receptor on the cell, necessary for viral attachment. This drug is a CCR5 antagonist. Some viral strains use CXCR4, an alternate co-receptor, for entry. A tropism assay is needed to confirm that the patient s virus uses only CCR5 for entry. Integrase Inhibitors block viral replication by preventing the incorporation of viral DNA into the host genome. Integrase inhibitors decrease the ability of the enzyme integrase to facilitate this vital step in HIV replication. Investigational antiretroviral therapies. The list of antiretroviral agents continues to grow as clinical trials provide new options for treatment. Information on clinical trials can be obtained from resources listed in the back of this sourcebook. ART Regimens Combination therapy with at least 3 active antiretroviral agents is currently recommended for HIV treatment. Preferred and alternate regimens are outlined in Table 14. Patients need to be aware that multi-drug regimens function as a whole, and that missing or stopping any of the medications can seriously jeopardize treatment Table 13. Medication Adherence Strategies to increase adherence Establish patient-provider rapport Educate and review goals of treatment, significance of labs (CD4+ T cells and viral load), and issues of resistance in the context of adherence Assess and monitor for depression, active drug or alcohol use, and other mental health issues Inquire routinely about social issues including housing, employment, and relationships Ask which medications the patient is taking and how they are taken at each appointment (use pictures of medications whenever possible) Ask about missed doses at each appointment and why doses were missed Do not be punitive or judgmental about missed doses, instead, use it as an opportunity to strategize with the patient Use pill boxes, monitor prescription refills, and/or consider pill counts if patient agrees Integrate HIV medications into the patient s daily routines Simplify regimens whenever possible Prepare patient for potential side effects Ask about issues of cost and access to medications Consider eliciting the help of a pharmacist and make other referrals as appropriate Use peer educators and/or treatment advocates Major factors that decrease adherence Mental health issues Active dependence on drugs and alcohol Undesirable or intolerable side effects effectiveness and future options. Complex decisions about when and how to initiate ART are best made during clinician-patient interactions. A careful assessment of patient readiness, goals, barriers, support, ability to adhere to treatment, and clinical status are important in this process. Providers with limited HIV experience should consult a specialist before initiating therapy. Not all patients can tolerate, adhere to, or achieve an undetectable viral load with combination therapy. Partial viral suppression (i.e., more than one-half log reduction in viral load) has been shown to provide clinical benefit, although partial suppression supports the development of drug resistance that can ultimately lead to treatment failure and disease progression. Monotherapy and dual therapy provide only partial suppression over time and are, therefore, not recommended. Factors that contribute to resistance include pre-existing resistance, inappropriate drug combinations, previous exposure to ART agents (especially in partially suppressive regimens), and patient non-adherence. Specific recommendations regarding dosing considerations are discussed in Appendix B. 16

25 Drug interactions can occur between many of the antiretroviral agents. Assessments for toxicities should be ongoing. See the guidelines or consult a specialist for details on drug interactions. Evaluating Therapy Response to treatment should be assessed 2-8 weeks after initiation of ART with a CD4+ T cell count and viral load analysis. Adjustments should be made if the viral load does not decrease during that time period. Fully successful regimens should reduce HIV levels to undetectable within 4-6 months. Viral loads should be monitored every 3-4 months in the stable patient. Current viral load assays may detect small amounts of virus in some patients; these low levels may not be indicative of risk for treatment failure. Virologic failure is defined in the DHHS guidelines as a confirmed and sustained HIV viral load of greater than 200 copies/ml. CD4+ T cell counts are generally measured at the same time. Monitoring intervals are recommendations; individual circumstances may require flexibility. Over the course of treatment, some patients with an initial good response to therapy may begin to show decreases in CD4+ T cell counts and increases in HIV viral loads, indicating a failure of the therapeutic regimen. Viral load assessments can be used as indirect measures of drug failure from resistance, patient non-adherence, inadequate absorption (e.g., due to vomiting or diarrhea), or adverse drug interactions. Discussions with the patient should include an honest appraisal of adherence to the medication regimen and adverse effects. The patient s medications should be reviewed to identify or rule out potential drug interactions that could reduce ART efficacy or exacerbate adverse effects. Table 14. ART Regimens Recommended for Treatment of HIV-1 Infection in ART-Naïve Patients Regimens are based on combination therapy, and generally contain 1 NNRTI with 2 NRTIs OR a single ritonavir-boosted PI with 2 NRTIs Preferred Regimens (adapted from DHHS 2011 Guidelines Table 5a) Preferred regimens for non-pregnant patients are arranged by order of FDA approval of components other than nucleosides, thus, by duration of clinical experience. Recommended dosing regimens illustrated. NNRTI-based regimen: EFV (QD) efavirenz PI-based regimens: ATV/r (QD) atazanavir + ritonavir DRV/r (QD, if ART naïve) darunavir + ritonavir Integrase Inhibitor-based regimen: RAL (BID) raltegravir Changing therapy can be a complex process, but general recommendations are presented in Table 15. When changing or modifying ART regimens, clinicians are urged to be conservative and take the time needed to make well-informed decisions with their patients based on treatment guidelines and in consultation and collaboration with HIV-experienced clinicians. Ideally, a new regimen should consist of three or more active drugs from at least + TDF/FTC tenofovir/ emtricitabine Principles for use of ART in pregnant women Start prior to second trimester, if possible Continue prior regimen if effective and well-tolerated Include 1 or more NRTIs with high levels of transplacental passage Account for teratogenicity and results of resistance testing Commonly used: LPV/r (BID) + ZDV/3TC lopinavir/ritonavir + zidovudine/lamivudine *Preferred regimens listed above. Alternative regimens may be considered based on resistance profile, tolerability, and patient preference. A list of alternative and acceptable regimens can be found at Table 15. Guidelines for Changing an ART Regimen with Suspected Drug Failure Criteria for changing therapy: Suboptimal reduction in plasma viremia after initiation of therapy Declining CD4+ T cell count After suppression to undetectable levels, repeated detection of viremia > 200 copies/ml Clinical deterioration Clinical considerations: Distinguish between the need to change a regimen due to drug intolerance or inability to adhere vs. failure to sustain viral suppression. Multiple factors should be considered when changing regimens, including results from resistance testing and medication history. Resistance testing may provide valuable information as new regimens are considered. Timing of resistance tests is important for interpretation. Although an undetectable viral load is the goal, some patients have limited options for new regimens; in some of these cases it is rational to continue a prior regimen if partial viral suppression was achieved and if alternatives are limited. For patients with limited options (resistance or intolerance), combinations of 4 or more medications are sometimes used. Cross-resistance may be seen with a number of drugs in the same class. Clinicians with less HIV-care experience should consult with HIV specialists when initiating or adjusting ART regimens. 17

26 two different classes. Remember: using a new agent for a patient does not always mean it will be effective due to cross-resistance of medications. Patient ART history, HIV viral load, and amount of drug resistance all contribute to decisions regarding management of the failing regimen. Criteria for the interpretations of genotypic and phenotypic resistance tests evolve constantly and consultation with an HIV expert is recommended. Prophylaxis for Opportunistic Infections This section contains general prophylaxis recommendations for common OIs. Some clinicians also advocate prophylaxis for a variety of other OIs. Referral to expert clinicians and review of the DHHS Guidelines is recommended (see Bibliography). Figure 5 shows CD4+ T cell counts at which various OIs typically occur. An effective response to ART provides important protection Prophylaxis can be discontinued in patients once the CD4+ T cell count is > 200 cells/mm³ for 3 months. All patients who have had prior PCP should be on secondary prophylaxis. The guidelines for secondary prophylaxis may vary from those of primary prophylaxis and it is best to refer to the guidelines (see Bibliography). Prophylaxis is also initiated for any occurrence of PCP with CD4+ T cells > 200 cells/mm³. The preferred primary prophylactic intervention for PCP is oral trimethoprim-sulfamethoxazole (TMP-SMZ), one double strength tablet QD or one single-strength tablet QD. For patients with CD4+ T cell counts < 100 cells/mm³ and positive toxoplasmosis serology, one double-strength TMP- SMZ will also provide protection against toxoplasmosis. If TMP-SMZ cannot be tolerated, alternatives for PCP prophylaxis include dapsone, aerosolized pentamidine, or atovaquone. Dapsone should not be administered if a patient is G6PD deficient. Approximately 25% of patients will not tolerate TMP-SMZ and may develop rash, fever, or elevated liver enzymes. Gradual initiation has been shown to decrease the incidence of rash. It may be preferred to initiate TMP- SMZ prior to starting ART as both interventions may be associated with adverse events and the etiology may be difficult to determine if both are started at the same time. Some patients will experience bronchospasm following pentamidine therapy. This can usually be treated symptomatically, but is occasionally severe enough to require discontinuation of the drug. Repeated exposure to pentamidine may be harmful for administering clinicians. Inhalation therapy should be done in a respiratory therapy setting that can provide safe containment of aerosolized and exhaled pentamidine. Inhaled pentamidine using alternate nebulization devices for administration is not recommended. from OIs. In situations where patients do not respond well to ART, or where the CD4+ T cell count is below certain thresholds, prophylaxis with other medications is indicated. In many cases, once immune reconstitution has occurred and is sustained, prophylaxis can be discontinued. See Table 16 for some of these guidelines. Pneumocystis jiroveci Pneumonia (PCP) Primary prophylaxis is intended to prevent the first episode of PCP and is begun or reintroduced when the CD4+ T cell count is 200 cells/mm³ or with a history of PCP. Prophylaxis should be considered if the CD4+ T cell proportion is < 14%, or if an AIDS-defining illness occurs. Herpes Simplex Virus (HSV) Infection and Varicella Zoster Virus (VZV) Infection Patients who have frequent or severe recurrences of HSV may benefit from suppressive therapy with acyclovir, famciclovir, or valacyclovir. If exposed to chickenpox or shingles, patients with no previous history of chickenpox or shingles or without detectable VZV antibody, should receive prophylaxis with varicella zoster immune globulin (VZIG). This should be administered as soon as possible but within 96 hours of close contact with chickenpox or shingles. Although there is now a zoster vaccine, it is a livevirus vaccine and not currently used in HIV care (see Table 20 in Part 3). 18

27 Infection P. jiroveci pneumonia (PCP) M. avium complex (MAC) T. gondii - toxoplasmosis M. tuberculosis (MTB, TB) Herpes simplex (HSV) Table 16. Prevention of Opportunistic Infections Indication to Indication to Preferred Prophylaxis Initiate Discontinue CD4+ < 200 CD4+ > 200 TMP/SMZ one double strength cells/mm³ or cells/mm³ for > tablet QD CD4% < 14%, 3 months TMP/SMZ one single strength history of thrush tablet QD or AIDS-defining illness CD4+ < 50 cells/mm³ Immunoglobulin G antibody to toxoplasma and CD4+ < 100 cells/mm³ Positive PPD, 5 mm without active TB or clear history of untreated positive PPD, or + IGRA *The distinction between active vs. latent TB must be made prior to initiating treatment Frequent or severe recurrences CD4+ > 100 cells/mm³ for > 3 months CD4+ > 200 cells/mm³ for > 3 months See guidelines Azithromycin 1200 mg weekly Clarithromycin 500 mg QD TMP/SMZ one double strength tablet QD INH 300 mg QD + pyridoxine 50 mg QD x 9 months not under direct observational therapy (DOT) INH 900 mg twice weekly + pyridoxine 100 mg twice weekly, DOT x 9 months INH 15 mg/kg rounded to nearest 50 or 100 mg; max 900 mg + rifapentine ( 50.0 kg, use 900 mg) once weekly, DOT x12 weeks* *The use of INH +RPT weekly x 12 weeks under DOT is limited to otherwise healthy PLWH not currently on ART. Acyclovir 400 mg BID Famciclovir 250 mg BID Alternate Prophylaxis Dapsone 100 mg QD Aerosolized pentamidine 300 mg/monthly Atovaquone 1500 mg QD Azithromycin 5 mg/kg (max 250 mg) QD Rifabutin 300 mg QD TMP/SMZ one single strength tablet QD Dapsone 50 mg QD + pyrimethamine 50 mg weekly + leucovorin 25 mg weekly Dapsone 200 mg weekly + pyrimethamine 75 mg weekly + leucovorin 25 mg weekly Atovaquone 1500 mg QD ± pyrimethamine 25 mg QD + leucovorin 10 mg QD See guidelines Valacyclovir 500 mg BID Mycobacterium avium Complex (MAC) The incidence of MAC infection increases about 20% each year after an AIDS-defining diagnosis in patients not receiving ART with CD4+ T cell counts < 50 cells/mm³. Individuals with CD4+ T cell counts < 50 cells/mm³ should be started on primary prophylaxis. Prophylaxis should be discontinued when CD4+ T cell counts increase to > 100 cells/mm³ for more than 3 months. Current guidelines recommend prophylaxis for individuals who meet the above criteria with azithromycin 1200 mg by mouth once a week or clarithromycin 500 mg by mouth BID. Many specialists prefer the former because of ease of dosing, lower cost, and fewer drug interactions with PIs. Alternatives include rifabutin, or azithromycin plus rifabutin. Seek consultation when using rifabutin, as its use is limited by multiple drug interactions. M. tuberculosis (MTB, TB) Active TB may develop relatively early in HIV infection and has a predilection for extrapulmonary sites. Because of this, any patient with (a) a positive PPD of at least 5 mm induration, or (b) a positive result on IGRA who does not have active TB, or (c) a clear history of an untreated 19

28 positive PPD, should receive treatment for latent TB infection. This may be accomplished with isoniazid (INH) daily for 9 months without DOT. For patients where adherence to a daily regimen is not possible, DOT of INH twice weekly is an alternative regimen. For individuals not currently on ART, the use of INH with rifapentine once weekly with DOT for 12 weeks can be considered. Pyridoxine should be co-administered with INH because of the risk of peripheral neuropathy. If there is resistance to INH, a 4-month regimen of either rifampin or rifabutin may be used. The decision to use a regimen containing either rifampin or rifabutin should be made with consideration of potential drug interactions with ART. The treatment of resistant latent TB or active TB should be done in conjunction with a specialist. T. gondii Prophylaxis against toxoplasmosis is appropriate for patients who have antibodies to the organism when CD4+ T cell counts are below 100 cells/mm³. Prophylaxis against both toxoplasmosis and PCP consists of TMP-SMZ, one double strength tablet QD. Alternatives include TMP-SMZ, one single strength tablet by mouth QD; dapsone, 50 mg by mouth QD plus pyrimethamine, 50 by mouth weekly plus leucovorin, 25 mg by mouth weekly; or atovaquone, 1500 mg by mouth QD with or without pyrimethamine, 25 mg by mouth daily plus leucovorin, 10 mg by mouth QD. Once patients respond to ART and their CD4+ T cell counts are > 200 cells/mm³ for more than 3 months, prophylaxis can be stopped. It should be restarted if the CD4+ T cell counts drops to < cells/mm³. Complications Associated with HIV Infection and ART Various morphologic and metabolic abnormalities have been described in PLWH. This is a heterogeneous group of conditions of varying etiologies. Prior to the initiation of ART, patients should be counseled about potential body fat and metabolic changes. Emphasis should be placed on the benefit of ART despite the potential for metabolic problems. Fat Redistribution Disorders A variety of morphological changes related to fat distribution have occurred in conjunction with HIV infection. These body fat changes can include the loss of subcutaneous fat in the face, extremities, and/or buttocks, as well as truncal fat and/or dorsocervical fat accumulations. The etiology is multifactorial, but ART and long-term HIV infection contribute to the problem. Physical body changes are distressing to many patients, but problems associated with lipodystrophy are more than cosmetic. Any side effect can have an adverse effect on adherence to ART, especially changes that affect body image. In addition, truncal obesity in uninfected populations is associated with increased rates of cardiovascular morbidity and mortality (problems that are also seen in patients with chronic HIV infection), and dorsocervical fat accumulation ( buffalo hump ) can compress the cervical spine, resulting in pain and the need for surgical removal of excess fat. Lipid Abnormalities Clinicians should develop and use consultation and referral systems with specialists in HIV care to improve diagnosis of HIV-related conditions and the quality and quantity of patients lives. Chronic HIV infection, genetic factors, lifestyle, and ART all contribute to dyslipidemia in PLWH. Certain ART medications are associated with increased levels of triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as decreased levels of highdensity lipoprotein (HDL) cholesterol. All patients should have fasting lipid profiles prior to beginning or changing ART. Profiles should be repeated 3-6 months after starting or switching therapy, and annually thereafter. Routine periodic assessments of these clinical parameters should be used to guide therapeutic decisions. In general, guidelines from the National Cholesterol Education Program can be used to manage dyslipidemia in PLWH. For patients with dyslipidemia, a combination of therapeutic lifestyle changes and medication may be needed to reach lipid goals. Fenofibrate, gemfibrozil, and omega-3 fatty acids can be used to lower triglycerides. Statins are effective for lowering LDL, but many statins interact with ART, especially the PIs. Pravastatin and atorvastatin have the fewest drug interactions and should be used in patients on PIs with elevated LDL. Patients should be started on the lowest dose and monitored carefully for liver toxicity and rhabdomyolysis. Hyperglycemia and Insulin Resistance Hyperglycemia and insulin resistance are associated with ART (specifically PIs), lifestyle, and genetic factors. Fasting or random plasma glucose should be assessed prior to starting ART and every 3-4 months after initiating therapy. When diabetes occurs in the setting of HIV treatment, therapy as indicated in non-hiv clinical settings should be considered and initiated. Diet and exercise regimens can be prescribed, but medications, including oral medications or injected insulin, may be required. Patients with diabetes, dyslipidemia, and hypertension should be treated and ideally meet target levels for diabetics. Refer to an endocrinologist as needed. 20

29 Weight Loss Weight loss is a multifactorial problem related to inadequate energy intake, metabolic dysregulation, side effects of medications, malabsorption syndrome, and/or infectious processes related to HIV and opportunistic diseases. All PLWH need nutritional assessment and counseling. Referral to a dietician early in the disease process helps many patients deal with nutrition issues. Other referrals (i.e., for mental health counseling or economic assistance) may also be needed. If body fat is proportionally low in relation to total body mass, simply increasing the daily caloric intake may improve the situation. Dietary supplements and appetite stimulation agents, such as megestrol acetate or dronabinol, may be helpful. Symptom Evaluation in the HIV-Infected Patient Diagnosis and treatment of opportunistic conditions associated with HIV can be difficult. Common causes of signs and symptoms seen in PLWH are listed in Table 17. Pulmonary Manifestations As a general rule, any pulmonary symptom, even if mild, warrants evaluation. The CD4+ T cell count influences the extent of the evaluation. Influenza, viral infections, fungal infections, mycobacterial infections, and non-infectious causes, such as congestive heart failure and pulmonary embolism, should be included in the differential for evaluation of pulmonary symptoms. A chest x-ray is usually recommended. It is important to consider that more than one pathogen might be present. Induced sputum samples can aid in the identification of the infectious organism. Other conditions, such as pulmonary KS, will require a lung biopsy for diagnosis. Patients with a CD4+ T cell count below 200 cells/mm³ are at an increased risk for acquiring PCP. The introduction of prophylactic medications and widespread use of ART has greatly reduced the incidence of PCP, however, it Eosinophilic folliculitis Folliculitis Itchy red bump disease Molluscum contagiosum remains the most common OI in persons infected with HIV. The symptoms of PCP are often subacute and include lowgrade fevers, dyspnea, and dry cough. A chest x-ray will usually reveal diffuse infiltrates. In mild cases, the chest x-ray may even be normal. Bacterial pneumonias also occur much more frequently in this patient population, and often present differently than PCP. High fever, productive cough, and symptoms with an acute onset are characteristic of bacterial pneumonia. A chest x-ray in this case will reveal focal infiltrates. As there can be several causes of pulmonary symptoms in persons infected with HIV, evaluation for pulmonary TB is necessary for both public health and personal health reasons. It is appropriate to treat patients empirically for suspected pulmonary conditions. For a person with a very low CD4+ T cell count and evidence of pneumonia, it is appropriate to begin empiric treatment for PCP and bacterial pneumonia while awaiting lab results or making referral arrangements. In settings when the patient is very ill and diagnostic procedures are not immediately available, it is appropriate to begin broad-spectrum empiric coverage for PCP and bacterial infection (and even fungal infection, if suspected) until a more definitive diagnosis can be established. Table 17. Common Causes of Signs and Symptoms in HIV Cutaneous Diseases Pulmonary Diseases Syphilis Coccidioidomycosis KS Lymphoid interstitial Tinea pneumonitis in HSV infection children VZV infection CMV pneumonitis Viral warts Histoplasmosis Neurologic Diseases CMV encephalitis HIV-associated dementia Peripheral neuropathy Primary CNS lymphoma CMV retinitis HSV infection Ocular Diseases PML Syphilis T. gondii encephalitis Syphilis VZV infection Diseases Causing Lymphadenopathy Disseminated cat MAC scratch disease infection HIV infection TB Lymphoma Oropharyngeal Diseases Mucocutaneous candidiasis Aphthous ulcers Gingivitis HSV infection OHL KS Cyptococcal pneumonia TB PCP Bacterial pneumonia Diseases Causing Diarrhea Bacterial pathogenic diseases Clostridium difficile Cryptosporidiosis Strongyloidiasis MAC, disseminated Mucocutaneous candidiasis CMV esophagitis Esophageal Diseases Giardiasis Isosporiasis KS CMV colitis HSV esophagitis Diseases Causing General Wasting TB CMV Strongyloidiasis infection MAC, disseminated HIV infection Anal/Perianal and Genital Diseases Chlamydial infection HPV infection Genital warts Syphilis Mucocutaneous HSV infection candidiasis Gonorrhea 21

30 Neurologic Presentations It is estimated that more than 50% of PLWH develop some type of neurological disease, causing changes in affect, behavior, and/or cognition, particularly in late stages of HIV infection (see Table 18). Neurologic symptoms can, however, present early in the course of disease and are the chief presenting complaint in about 20% of cases. Minor cognitive impairment occurs in 20-40% of HIV-infected asymptomatic patients; more severe impairment may be seen in people with AIDS-defining illness. Evaluation of global CNS dysfunction should generally include imaging (either CT or MRI brain scan) to look for evidence of mass lesions or cortical atrophy, the latter of which is seen in HIV encephalopathy. A lumbar puncture following a CT may also help to determine etiologies. Successful treatment of HIV, in general, is the most effective treatment for HIV-associated cognitive deficits, dementia, and encephalopathy. Opportunistic infection or malignancy, however, should always be considered. Altered mental status can also be a manifestation of fungal meningitis, particularly coccidiodomycosis or cryptococcal meningitis. In addition, clinicians should always consider syphilis and a number of viral pathogens in the differential diagnosis. Space occupying lesions in the brain can manifest as focal findings on physical examination. The most common causes include CNS lymphoma, CNS toxoplasmosis, and PML. A presumptive diagnosis of CNS toxoplasmosis may be made by a positive serum toxoplasmosis IgG serology plus the characteristic ringenhancing lesion on CT. A brain biopsy is the definitive diagnostic procedure, but not always necessary. CNS lymphoma often presents as a single lesion and is seen more frequently in patients with advanced HIV disease. PML will usually demonstrate Table 18. Neurologic Manifestations Clinical Etiologic Agent or Disease Syndrome Cerebrovascular CMV disease HIV Infective endocarditis with emboli TB Treponema pallidum VZV Dementia HIV Treponema pallidum Encephalitis acute HIV infection CMV HSV West Nile virus Mass lesion in the brain Meningitis Myelopathy/ radiculopathy Peripheral neuropathy several lesions involving the white matter. Other causes of brain lesions should be included in the differential such as brain abscesses and neoplasm metastases. T. gondii JC virus (the cause of PML) Primary CNS lymphoma Cryptococcus neoformans HIV TB Treponema pallidum CMV HIV VZV Medications Toxins (alcohol, etc.) Vitamin deficiencies (B12, folate) Ocular Involvement CMV infection is the most common cause of retinitis and sight-threatening ocular disease associated with HIV. It occurs most often in patients with severe immunosuppression or CD4+ T cell counts < 50 cells/mm³. The incidence of this OI greatly declined with the advent of more effective combinations of ART. Other causes of retinitis include VZV, T. gondii, and HSV. Anterior uveitis can be a complication of syphilis. Diagnosis is usually established through a dilated eye exam performed by an HIV-experienced ophthalmologist. Cutaneous Manifestations The incidence of dermatologic manifestations in persons infected with HIV is close to 100%. Recurrent HSV and VZV are frequent causes of morbidity in HIV infection. Because of impaired immune response, the appearance of these conditions may be unusual, sometimes forming chronic, extensive, superficial ulcerated areas. Confirmation of the diagnosis by culture should be completed if available. Prolonged prophylaxis with oral acyclovir, famciclovir, or valacyclovir may prevent outbreaks, as lesions tend to recur when prophylactic medications are stopped. Minor afflictions of the skin are commonly seen in people with HIV infection. Cutaneous mycoses (tinea) are diagnosed and treated in the usual way. Xerosis is managed symptomatically. Seborrheic dermatitis is very common in this population, especially on the face. Ketoconazole or itraconazole cream applied topically may be effective for chronic seborrheic dermatitis. Molluscum contagiosum and veruccae may be extensive and are generally removed by excision or cryosurgery. KS is a proliferative condition of cells of vascular origin. It is seen almost exclusively in MSM and is caused by human herpes virus type 8 (HHV8). The appearance of purplish subcutaneous nodules is usually typical enough to permit a clinical diagnosis, but a biopsy is the definitive test if there is doubt about the nature of the lesion. The cutaneous form is seldom fatal, but visceral involvement, particularly gastrointestinal or pulmonary disease, carries a poor prognosis. Potent combination ART will often improve or resolve cutaneous KS without additional treatment. However, some cutaneous KS can be extensive, obstructing lymphatic flow and causing disfigurement. For extensive 22

31 lesions, further intervention is often needed. Several treatments are available, including radiation therapy, direct lesion injection with chemotherapy, and systemic chemotherapy. A decision to treat and selection of treatment modalities must be individualized with consideration of the patient s wishes and prognosis. Oral Manifestations Dental health professionals play an important role in comprehensive health care for PLWH; they are essential members of the treatment team. Several conditions associated with HIV, including candidiasis, OHL, and KS, can first appear inside the mouth. Because of this, dental professionals may be the first to suspect HIV infection and are instrumental in providing appropriate referrals for HIV testing, counseling, and clinical care. In fact, dental offices are often ideal sites for initial HIV antibody testing. Aggressive prophylactic oral care can reduce difficulties related to oral pathology, medical, nutritional, psychological, and social complications; it can also improve immune function. In HIV disease, oral health can decline as a result of systemic illness, in conjunction with drug use, or when socioeconomic factors prevent access to care. A combination of active oral disease and lack of dental care can cause debilitating oral pain, impaired nutrition, aesthetic concerns, and the need for emergency treatment. Delays in oral health care can lead to tooth loss in immune compromised patients who will also be at risk for complications from invasive oral procedures. All of these may lead to negative repercussions to the patient s overall health, self-esteem, independence, or ability to work. Advances in ART have been associated with better oral health in PLWH. While this is encouraging, it does not decrease the need for proactive dental care, routine prophylactic appointments, and aggressive intervention for developing problems. As always, consultation and referral are appropriate when caring for PLWH with complex pathologies. 23

32 24

33 Primary Care and Disease Prevention In the United States, the availability of effective ART and access to health care has extended the life span for many PLWH. With longevity, however, comes a need to address primary care issues including, but not limited to, vaccinations, cancer screenings, and screening for and management of CVD and diabetes. Primary care providers play an integral role in assuring that PLWH receive appropriate and timely care. In general, guidelines for uninfected patients should also be followed for PLWH. Special considerations are necessary for vaccinations, cervical cancer screening, anal cancer screening, and for patients on ART. Table 19 addresses health care maintenance for patients with HIV. are imperative. Patients should be advised of appropriate weight management, diet, exercise, and health care maintenance. Important considerations for PLWH include treatment fatigue and feeling overwhelmed by chronic and complex medical conditions. Consistent support and Considerations for an Aging Population In the United States, the population of PLWH is aging, highlighting the need for ongoing primary care management. Many patients who were initially infected in their 30s and 40s are aging into their 50s and 60s and, as a result, are experiencing illness associated with aging, long-term HIV infection, and co-morbidities. Considerations for this aging population are similar to those of people without HIV infection and, as with all populations, routine prevention and screening 25

34 education from an integrated health care team including physicians, nurses, pharmacists, dental professionals, social workers, and mental health professionals can improve coping skills and alleviate stress. Immunizations Primary prevention of infectious diseases through immunization is recommended in many cases, as significant morbidity and mortality in PLWH is associated with preventable illnesses (see Table 20). In general, inactivated vaccines are safe, but live virus vaccines are often restricted in patients with a CD4+ T cell count < 200 cells/mm³. Typically, patients have the best response to immunizations when the CD4+ T cell count is > 200 cells/mm³. Administration of immunizations prior to immune reconstitution or when the CD4+ T cell count is < 200 cells/mm³ is not recommended with the exception of the annual influenza vaccine. Influenza and Pneumococcus Immunization with pneumococcal polysaccharide vaccine and inactivated influenza vaccine (in season) is appropriate at all stages of Table 20. Recommended Vaccines in HIV-infected Adults Recommended for ALL HIV-Infected Adults Influenza inactivated, currently only in intramuscular injection formulation (annually) Pneumococcal polysaccharide (every 5 years) Tetanus, diphtheria, acellular pertussis (Tdap; every 10 years) Hepatitis A (test for previous exposure and immunity) Hepatitis B (test for previous exposure, acute infection, and immunity) Hepatitis A/B (Twinrix combination vaccine, series of 3 injections) Recommended for SOME HIV- Infected Adults Meningococcal (with appropriate risk factors) Measles, mumps, rubella (MMR; with appropriate risk factors) Varicella (CD4+ T cell count > 200 cells/mm³) HIV. In more advanced HIV disease, the immune response to these antigens may be less than that of an immune competent person, but the immunizations should still be given. If the pneumococcal vaccine was initially given when the patient s CD4+ T cell count was < 200 cells/mm³, revaccination is recommended once the CD4+ T cells are > 200 cells/mm³. and HCV respectively. Being infected with one type of hepatitis is not a contraindication for being vaccinated against others. PLWH co-infected with HBV and/or HCV should be vaccinated against HAV, and those co-infected with HCV should receive the HBV vaccine if not immune. PLWH who are hepatitis co-infected should be counseled to avoid alcohol and educated about risk behaviors and ways to reduce transmission. A discussion of the HIV-infected person who is co-infected with chronic HBV and HCV is beyond the scope of this sourcebook (see resources). Treatment of HBV and HCV can be complex and should prompt consultation and/or referral to a specialist. Tetanus and diphtheria (Td)/Tetanus, diphtheria, acellular pertussis (Tdap) Td and Tdap vaccines are safe in PLWH. For patients due for a booster, Tdap should be given in place of Td. Measles Measles vaccine is a live virus vaccine, but it appears safe to administer to certain PLWH who are not immune to measles. It is not recommended in patients with a history of an AIDS-defining illness, with symptoms of HIV, or a CD4+ T cell count < 200 cells/mm³. A complete discussion of the appropriate age groups for whom measles immunization is recommended is beyond the scope of this sourcebook, but the information can be readily obtained from a local health department. Varicella The varicella vaccine is a live attenuated vaccine used for the prevention of varicella infection. Current guidelines state that varicella vaccine may be considered in adults and children older than 8 years of age or with a CD4+ T cell count > 200 cells/mm³ who have no evidence of previous VZV infection. PLWH who are VZV seronegative and exposed to a person with chickenpox or shingles should receive post-exposure prophylaxis with VZV immune globulin (VZIG) within 96 hours of exposure. Hepatitis Hepatitis can be a major contributor to the morbidity and mortality of co-infected individuals. Immunization should be offered to all at-risk patients without evidence of immunity to HAV and/or HBV. Approximately 10% and 15-30% of PLWH are chronically infected with HBV Zoster The zoster vaccine is a live attenuated vaccine used to prevent herpes zoster infection. There is a lack of data on the use of this vaccine in persons with HIV and it is currently not recommended for persons with HIV. 26

35 Cardiovascular Complications and HIV Prevention As PLWH continue to age, there is growing need to evaluate cardiovascular risk and implement primary prevention measures. Estimating cardiovascular risk helps in the clinical management of patients at risk for cardiovascular events. Focus should be given to modifiable risk factors, including tobacco use, blood pressure, and cholesterol levels. The benefits of aspirin therapy in prevention of CVD should be assessed in men ages and women ages The potential harms of implementing this therapy should also be evaluated, including the risk of gastrointestinal hemorrhage, particularly in persons using NSAIDs regularly or with a history of gastric ulcers. Metabolic Syndrome The increased prevalence of metabolic syndrome in PLWH has drawn attention to the need for providers to identify individuals at risk for the development of CVD. Metabolic syndrome is comprised of (a) elevated fasting triglycerides, (b) low HDL cholesterol levels, (c) increasing abdominal obesity, (d) elevated fasting glucose levels, and (e) hypertension. Over time, ART is thought to induce insulin resistance, particularly when PIs are used. Longer exposure to ART and increased survival times contribute to the development of metabolic syndrome. Dyslipidemia Dyslipidemia is an important risk factor that needs to be addressed as part of the primary care of PLWH. An association between many antiretroviral agents and dyslipidemia has been found, particularly with PIs, although the effect varies greatly between medications within this class. Ritonavir, particularly at higher dosages, has been associated with significant elevations in triglycerides. The use of simvastatin or lovastatin is contraindicated for those receiving ART, and caution should be used with several other lipid-lowering agents, as there can be significant drug-drug interactions. As recommended for uninfected people, lifestyle modifications are first-line treatments that should be implemented prior to or concurrently with pharmacologic interventions. Such modifications include limiting saturated fat, decreasing dietary cholesterol, and increasing physical activity. Fish oil is often used for the treatment of dyslipidemia in this population as it is well tolerated with minimal drug-drug interactions. An endocrinologist with experience treating dyslipidemia in PLWH should be consulted if available. Malignancies and HIV PLWH are at increased risk of developing cancers and should be screened accordingly. While the risk is higher for KS, non-hodgkin lymphomas, and cervical cancer, all of which are classified as AIDS-defining cancers by the CDC, the number of cases of AIDS-defining cancers has been steadily declining with the advent of highly effective ART. In contrast, the rates of non-aids defining malignancies, including anal and oropharyngeal cancers, liver cancer, lung cancer, and Hodgkin lymphoma have been steadily increasing in PLWH. There is an association between non- AIDS defining malignancies and infections. For instance, anal and oropharyngeal cancers are associated with HPV, and liver cancer with HBV and HCV. Likewise, smoking is more common in PLWH, placing them at a higher risk of developing lung cancer. While impaired immunity seems to play a role in the development of certain malignancies, the extent to which immune suppression influences the development of cancer has yet to be determined. Prolonged immune suppression seems to be associated with an increase in the incidence of cancer, but the level of immune suppression at which risk is increased is unknown. Traditional risk factors, including tobacco and alcohol use, sun exposure, and age also contribute to higher incidences of cancer. Primary care providers should focus on early detection and prevention. Recommendations for screening as used in the general population should be followed. Age- and gender-specific recommendations for screening and early detection are available from the U.S. Preventative Task Force. Prevention methods are also similar to those offered to uninfected patients. The focus here is on smoking cessation and prevention and treatment of underlying infections such as HBV, HCV, and HPV. U.S. Preventive Task Force recommendations for screening and early detection can be found at uspreventiveservicestaskforce.org/adultrec.htm#cancer Bone Loss and HIV The relationship between HIV infection, ART, and bone loss has become an issue of concern for providers caring for PLWH. Bone loss, including osteopenia and osteoporosis, is associated with an increased risk of fractures. Several studies have demonstrated low bone mineral density (BMD) in PLWH, but the cause remains unclear. The effect of ART on bone loss is unknown, but there is general consensus that some BMD loss can be expected in the first 18 months of ART before reaching a point of stabilization. Traditional risk factors, such as body mass index (BMI), vitamin D deficiency, and age are also predictors of lower BMD in PLWH. Social and medical histories should be taken into account as lifestyle factors can also contribute to lower BMD, including smoking, alcohol use, and effects of 27

36 medications. Research is currently addressing the effect of HIV infection on bone loss, as well as causal relationships between specific drug therapies and bone loss. Similar to minimizing cardiovascular risk in this population, modifiable factors should be addressed until more definitive conclusions have been drawn as to the effect of specific ART on bone loss. Vitamin D synthesis and metabolism are also disrupted in this population through multiple mechanisms, including HIV infection itself, and the use of certain antiretroviral agents. As vitamin D deficiency is associated with heart disease, dyslipidemia, and diabetes, health care providers should consider screening PLWH for vitamin D insufficiency or deficiency. Screening for osteoporosis should be done according to guidelines for uninfected patients. Treatment for osteopenia in females, if indicated, should include calcium and vitamin D supplementation, weightbearing exercise, and modification of risk factors. If osteoporosis is present, consideration should be given to bisphosphonate therapy. U.S. Preventive Task Force recommendations for screening for osteoporosis can be found at uspreventiveservicestaskforce.org/uspstf10/osteoporosis. htm Women s Health Providers caring for women infected with HIV must address HIV-related health concerns across the lifespan. The risk of vertical transmission, or maternal-to-child transmission (MTCT) of HIV, has decreased dramatically over the last several years because of targeted HIV testing and treatment. Family planning and reproductive health issues need to be addressed consistently with all HIV-infected women. Other gynecologic issues, including abnormalities in menstrual cycles, STIs, neoplasias, and menopause, also need to be addressed. A work-up for irregular menses should be similar to that in uninfected women, taking into account the many causes of menstrual abnormalities including, but not limited to, pregnancy, dysfunction in the hypothalamicpituitary-ovarian system, menopause, drug use, stress, BMI, hematologic abnormalities, infection, and the direct effects of HIV. Invasive cervical cancer is an AIDS-defining illness. HIV-infected women have a greater prevalence of cervical dysplasia and monitoring through Pap smears should occur at more frequent intervals than are used for uninfected women. Many factors can contribute to the increase in cervical dysplasia, including immune suppression, and an increased prevalence in all types of HPV. Even in women who are not sexually active, HPV reactivation from past exposure can occur particularly with lower CD4+ T cell counts and elevated viral loads; all HIV-infected women should, therefore, be screened regularly, regardless of whether they are sexually active or not. The current recommendation is for women to be screened with Pap smears at 6-month intervals during the first year after an HIV diagnosis, and annually thereafter if cytology is normal. Contraception choices for women with HIV should protect them from other STIs, minimize unplanned pregnancies, and limit the risk for HIV transmission. Hormonal contraceptives should be used cautiously and drug interactions taken into account, particularly with ART; if possible, more than one method of contraception should be used. Intrauterine devices do not have the same risk of drug interactions as seen with oral contraceptives and are one option for contraception. Barrier methods should be encouraged to limit HIV transmission risks to the woman s sex partner(s). Menopause issues are also of concern as the population of HIV-infected women continues to age. Hormone replacement therapy should be used cautiously, similarly to uninfected women. While women may find relief from hot flashes, irritability, and sleep disturbances, there is also an increased risk for breast cancer, stroke, pulmonary embolism, and CVD. Progestin-only regimens may help with hot flashes, although the long-term effects are unknown. The use of non-hormonal lubricants can assist with urogenital atrophy. For women with osteoporosis, bisphosphonates should be considered to minimize risk of fractures. Sexually Transmitted Infections Screening for STIs should be performed annually with all PLWH, and more frequently if warranted. Genital ulcer disease can facilitate the transmission of HIV infection, and should, therefore, be identified and treated as appropriate. HSV and syphilis are associated with increased rates of HIV transmission. The risk of developing pelvic inflammatory disease (PID) in women is similar to the general population; however, the level of immune suppression in women with HIV may complicate the course of treatment. Drugs and HIV Drug use continues to be associated with the spread of HIV infection. Drug use and abuse contributes to the transmission of the virus as drug networks and sexual circles often overlap. HIV is then readily spread by sharing contaminated drug-use paraphernalia and by high-risk sexual behavior with other IDUs or with sex partners who do not inject drugs. A higher prevalence of STIs, such as gonorrhea, chlamydia, and syphilis, is notable among IDUs and can facilitate transmission of HIV. Co-morbid conditions are often identified in individuals who use drugs 28

37 and are infected with HIV, including HCV, HBV, STIs, and psychiatric conditions. Clinical management can be complicated by these often chronic, co-morbid conditions. Interventions should address addiction and psychiatric conditions, and medical co-morbidities simultaneously for the best health outcomes. Substance abuse, including drugs and alcohol, is consistently associated with poorer outcomes in HIV infection. Drug dependence is important to recognize and treat as appropriate. The barriers to maintaining good virologic control are often different than in non-users. Socioeconomic factors, transient lifestyles, and lack of social support create challenges that are important to address as these problems can decrease patient abilities to engage and stay in care, adhere to medication protocols, and use measures to decrease the risks of HIV transmission to others. Psychotherapy, planning for relapse, and pharmacologic management of co-morbid psychiatric conditions can contribute to a more successful patientprovider relationship. Mental Health Issues in the Care of the HIV-Infected Patient Similar to other chronic diseases, HIV infection can be complicated by mental illness. A thorough mental health history should be taken during the initial visit, including a history of a diagnosed mental illness, medications, hospitalizations, suicidal ideation and attempted suicide, trauma, and assessment of current symptoms. See Table 21 for common psychosocial issues commonly faced by PLWH. Addressing the mental health needs of PLWH is a critical measure to optimize patient outcomes following an HIV diagnosis. Patients experience a time of increased stress and anxiety following the initial diagnosis of HIV, which can lead to self-destructive behaviors and cause delays in seeking care. Many patients, particularly when newly diagnosed, will have complex feelings about the diagnosis. An estimated 13-20% of PLWH have symptoms of posttraumatic stress disorder (PTSD) following an HIV diagnosis. Some PLWH will present with anxiety disorders, panic disorders, depression, personality disorders, or psychosis. Mental health needs can be complex and exacerbated by the HIV diagnosis and having to cope with a chronic illness. PLWH with an established diagnosis of mental illness should be encouraged to maintain or re-establish relationships with mental health professionals. Newly diagnosed patients may have an exacerbation of a pre-existing mental illness. Patients who develop mental health issues while in care for HIV infection should be referred to a mental health provider for evaluation. When available, it is important to use the expertise of mental health providers experienced in treating PLWH. Depression is often present in this patient population, with the prevalence estimated to be 19-45%. Depression can be difficult to recognize, as many of the symptoms of depression can be confused with side effects of medications or with a grief reaction to the HIV diagnosis and/or the change in life circumstances. Treatment of depression is similar to treatment in uninfected patients, and no clear delineation has shown that one antidepressant is superior to another. Attention should be given to the side effect profiles of antidepressants, drug interactions, and desired effects.treating depression is paramount to maintaining long-term adherence to therapy. There is also evidence that the immune response is blunted in PLWH with untreated depression. Insomnia may be a symptom of stress, anxiety, depression, or an adverse effect of ART. Patients should be screened for these conditions and educated about appropriate sleep hygiene (routines before bed, reduce stimulants, etc.). Sleep aids may be appropriate for some patients; however, caution should be used as patients can quickly develop dependency and tolerance to some medications. Medications such as diphenhydramine or trazodone have a low risk of dependency. Table 21. Psychosocial Issues for the Patient with HIV Infection Physical loss of physical strength hospitalization(s) sexuality Emotional self-esteem hopelessness/despair uncertainty anxiety embarrassment anger Social finances relationships sexuality Spiritual meaning of life death finding professional providers adherence to treatment regimens fatigue depression sadness fear loss of dreams and future plans independence/control leisure friends/family/community acceptance/hope spiritual practice spiritual connection changes and disturbances in body image substance use shock grief denial body image guilt self-blame social support discrimination stigma forgiveness suicide 29

38 Cognitive dysfunction, including HIV-associated dementia, is associated with severe immune suppression and a number of AIDS-defining conditions. Dysfunction can manifest in subtle ways and is easily missed by providers. The presence of minor difficulties with simple tasks, such as reading, basic math skills, or tasks requiring fine motor control, may not be obvious in typical clinical assessments. Effective ART is currently the best method to improve these symptoms. A model that incorporates integrated mental health services is preferred to support the psychiatric needs of this patient population. Mental illness and psychosocial stresses create barriers to consistent adherence to treatment regimens and clinical care. Clinicians must be constantly aware of these issues in order to assess problems and work with the client and the care team to find solutions. Consultation with and referral to mental health specialists should occur routinely. 30

39 Bibliography Aberg, J.A., Kaplan, J., Libman, H., Emmanuel, P., Anderson, J.R., Stone, V.E.,... Gallant, J.E. (2009) Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clinical Infectious Diseases, 49, doi: / Bartlett, J., & Gallant, J. (2007). Medical management of HIV infection. Baltimore, MD: Johns Hopkins University, Department of Infectious Diseases. Bhavan, K., Kampalath, A., & Overton, E. (2008). The aging of the HIV epidemic. Current HIV/AIDS Reports, 5, doi: /s Branson, B. (2010). The future of HIV testing. Journal of Acquired Immune Deficiency Syndromes, 55(Suppl. 2), S102-S105. doi: /qai.0b013e3181fbca44 Castilla, J., Sobrino, P., de la Fuente, L., Noguer, I., Guerra, L., & Parras, F. (2002). Late diagnosis of HIV infection in the era of highly active antiretroviral therapy: Consequences for AIDS incidence. AIDS, 16(14), Carr, A. (2003). Lactic acidemia in infection with human immunodeficiency virus. Clinical Infectious Diseases, 36(S2), S96-S100. doi: / Cejtin, H. (2008). Gynecologic issues in the HIV-infected woman. Infectious Disease Clinics of North America, 22, doi: /j.idc Centers for Disease Control and Prevention. (2005, January 21). Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States. Recommendations from the U.S. Department of Health and Human Services. Retrieved from or Centers for Disease Control and Prevention. (2009, April). Diagnoses of HIV Infection and AIDS in the United States and Dependent Areas, Retrieved from 9report/ Centers for Disease Control and Prevention. (2009, April 9). Guidelines for the prevention and treatment of opportunistic infections among HIV-infected adults and children 2009, recommendations of the National Institutes of Health, the Centers for Disease Control and Prevention, and the HIV Medicine Association of the Infectious Diseases Society of America. Retrieved from Centers for Disease Control and Prevention. (2012, March 27). Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Retrieved from Centers for Disease Control and Prevention. (2011, August 11). Guidelines for the use of antiretroviral agents in pediatric HIV infection. Retrieved from Centers for Disease Control and Prevention. (2011, August). High-impact HIV prevention: CDC s approach to reducing HIV infection in the United States. Retrieved from Centers for Disease Control and Prevention. (2007, March 28). HIV counseling with rapid tests. Retrieved from rt_counseling.htm Centers for Disease Control and Prevention. (2003, July 18). Incorporating HIV prevention into the medical care of persons living with HIV: Recommendations of the CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Retrieved from Centers for Disease Control and Prevention. (2003, April). Partner counseling and referral services guidance. Retrieved from or Centers for Disease Control and Prevention. (2001, June 29). Updates U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. Retrieved from Centers for Disease Control and Prevention. (2011, September 14). Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States Retrieved from pdf Centers for Disease Control and Prevention. (2006, September 22). Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Retrieved from Centers for Disease Control and Prevention. (2011, August). Strategic plan: Division of HIV/AIDS Prevention, 2011 through Retrieved from Centers for Disease Control and Prevention. (2005, September 30). Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. Retrieved from 31

40 Centers for Disease Control and Prevention. (2011, November 19). Vital signs: HIV prevention through care and treatment United States. Retrieved from 4.htm?s_cid=mm6047a4_w Chow, D.C., Day, L.J., Souza, S.A., & Shikuma, C.M. (2006). Metabolic complications of HIV therapy. HIV InSite Knowledge Base. Retrieved from The DAD Study Group. (2007). Class of antiretroviral drugs and the risk of myocardial infarction. New England Journal of Medicine, 356, Dao, C., Patel, P., Overton, E., Rhame, F., Pals, S.L., Johnson, C.,... Brooks, J.T. (2011). Low vitamin D among HIVinfected adults: Prevalence of and risk factors for low vitamin D levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clinical Infectious Diseases, 52(3), doi: /cid/ciq158 Dube, P., Stein, J.H., Aberg, J.A., Fichtenbaum, C.J., Gerber, J.G., Tashima, K.T.,... Glesby, M.J. (2003). Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trails Group. Clinical Infectious Diseases, 37, doi: / Gallant, J.E. (2004). HIV counseling, testing, and referral. American Family Physician, 70(2), Gallant, J.E., Adimora, A.A., Carmichael, J.K., Horberg, M., Kiahata, M., Quinlivan, E.B.,... Williams, B. (2011). Essential components of effective HIV care: A policy paper of the HIV Medicine Association of the Infectious Diseases Society of American and the Ryan White Medical Providers Coalition. Clinical Infectious Diseases, 53(11), doi: /cid/cir689 Girardi, E., Sabin, C., & Monforte, A.D. (2007). Late diagnosis of HIV infection: Epidemiological features, consequences and strategies to encourage earlier testing. Journal of Acquired Immune Deficiency Syndrome, 46(S1), S3-S8. doi: /01.qai b Grinspoon, S., & Carr, A. (2005). Cardiovascular risk and body-fat abnormalities in HIV-infected adults. New England Journal of Medicine, 352(1), Harrigan, P.R., Hogg, R.S., Dong, W.W.Y., Yip, B., Wynhoven, B., Woodward, J.,... Montaner, J.S.G. (2005). Predictors of HIV drug-resistance mutations in a large antiretroviral-naïve cohort initiating triple antiretroviral therapy. The Journal of Infectious Diseases, 191, doi: / Ho, J., & Hsue, P. (2009). Cardiovascular manifestations of HIV infection. Heart, 95, doi: / 01.CIR Hoy, J. (2011). Bone, fracture and frailty. Current Opinions in HIV and AIDS, 6, doi: /coh.0b013e Joint United Nation Programme on HIV/AIDS. (2010). Global report: UNAIDS report on the global AIDS epidemic. Retrieved from GlobalReport_full_en.pdf Johnson, S.C. (2011). HIV: The approach to the HIV-infected patient with specific symptom complexes/common presentations. Retrieved from Kahn, J.O., & Walker, B.D. (1998). Acute human immunodeficiency virus type 1 infection. The New England Journal of Medicine, 339(1), Landon, B.E., Wilson, I.B., McInnes, K., Landrum, M.B., Hirschorn, L.R., Marsden, P.V., & Cleary. P.D. (2005). Physician specialization and the quality of care for human immunodeficiency virus infection. Archives of Internal Medicine, 165, Ledergerber, B., Furrer, H., Rickenbach, M., Lehmann, R., Elzi, L., Hirshel, B.,... Weber, R. (2007). Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss cohort study. Clinical Infectious Diseases, 45, doi: / Lyles, C.M., Kay, L.S., Crepaz, N., Herbst, J.H., Passin, W.F., Kim, A.S.,... Mullins, M.M. (2007). Best-evidence interventions: Findings from a systematic review of HIV behavioral interventions for US populations at high risk American Journal of Public Health, 97(1), doi: /ajph Marks, G., Gardner, L.I., Craw, J., & Crepaz, N. (2010). Entry and retention in medical care among HIV-diagnosed persons: A meta-analysis. AIDS, 24, doi: /qad.0b013e32833f4b1b Office of National AIDS Policy. (2010, July). National HIV/AIDS strategy for the United States. Retrieved from Reznik, D. (2005). Perspective: Oral manifestations of HIV disease. Topics in HIV Medicine, 13(5), Sanders, G.D., Bayoumi, A.M., Sundaram, V., Bilir, P., Neukermans, C.P., Rydzak, C.E.,... Owens, C.K. (2005). Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. New England Journal of Medicine, 352, Sethi, A.K., Celentano, D.D., Gange, S.J., Moore, R.D., & Gallant, J.E. (2003). Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance. Clinical Infectious Diseases, 37, doi: / Shiels, M., Pfeiffer, R., Gail, M., Hall, H.I., Li, J., Chaturvedi, A.K.,... Engels, E.A. (2011). Cancer burden in the HIVinfected population in the United States. Journal of the National Cancer Institute, 103, doi: /jnci/djr07 32

41 Stone, V.E., Jordan, J., Tolson, J., Miller, R., & Pilon, T. (2004). Perspectives on adherence and simplicity for HIVinfected patients on antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes, 36(3), Wilkin, T., Glesby, M., & Gulick, R.M., (2006). Switching antiretroviral therapy: Why, when, and how. Retrieved from Winstanley, E. Gust, S., & Strathdee, S. (2006). Drug abuse and HIV/AIDS: International research lessons and imperatives. Drug and Alcohol Dependence, 82(Suppl. 1), S1-S5. Wohl, D., McComsey, G., Tebas, P., Brown, T.T., Gelsby, M.J., Reeds, D.,... Wanke, C. (2006). Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. Clinical Infectious Diseases, 43, doi: /

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43 Appendices & Resources 35

44 36

45 Appendix A. Occupational Post-Exposure Prophylaxis (PEP) Guidelines Treat exposure site. Wash areas exposed to potentially infectious fluids with soap and water as soon as possible after the exposure. Do NOT apply caustic agents or inject antiseptics or disinfectants into the wound. Exposed mucous membranes should be flushed with water and exposed eyes should be flushed with saline solution. Report and document. Report all occupational exposures immediately. Reports need to document the following: Exposure Type Small Volume - a few drops Large Volume - large blood splash HIV PEP for Mucous Membrane and Non-Intact Skin Exposures HIV- Infected Class 1 e.g., asymptomatic HIV infection or viral load < 1,500 RNA copies/ml Consider basic 2-drug PEP Recommend basic 2-drug PEP HIV-Infected Class 2 e.g., symptomatic HIV infection, AIDS, acute seroconversion, or known high viral load* Recommend basic 2-drug PEP Recommend expanded 3- drug PEP Infectious Status of Source Unknown HIV status e.g., source patient refuses testing or is unavailable Generally no PEP warranted; consider basic 2-drug PEP¹ for source with HIV risk factors² Generally no PEP warranted; consider basic 2-drug PEP¹ for source with HIV risk factors² Unknown source e.g., blood spill or bloody equipment that cannot be traced to a patient Generally no PEP warranted; consider basic 2-drug PEP¹ in settings where exposure to HIV likely Generally no PEP warranted; consider basic 2-drug PEP¹ in settings where exposure to HIV likely Date and time of exposure Details of the incident: where and how the exposure occurred, exposure site(s) on the body; if related to sharp device, the type and brand of device should be recorded Details of the exposure: type and amount of fluid or material, severity of the exposure Counseling, post-exposure management, and follow-up HIV- Negative e.g., source patient known to be uninfected No PEP warranted No PEP warranted ¹The designation consider PEP indicates that PEP is optional and should be based on an individualized decision between the exposed person and the treating clinician. ²If PEP is initiated and the source is later determined to be uninfected, PEP should be discontinued. *Seek expert consultation if drug resistance is a concern. Initiation of PEP should NOT be delayed pending expert consultation. Details about the exposure source: whether the source material is known to contain HIV; if source patient is HIV infected, determine stage of disease, viral load, history of ART, and antiretroviral resistance information Details about the exposed individual: HBV vaccination and vaccine-response status, other medical conditions, allergies, and medications Record circumstances of the exposure and PEP management in the exposed person s confidential medical record. Evaluate exposure. Evaluate the exposure for the potential to transmit HBV, HCV, or HIV based on the type of body substance involved and the route and severity of exposure. Exposures to any of the following through percutaneous injury or contact with a mucous membrane are situations that cause a risk for bloodborne transmission and require further evaluation: Amniotic fluid Blood Cerebrospinal fluid Pericardial fluid Peritoneal fluid Pleural fluid Semen Synovial fluid Vaginal secretions 37

46 Assess need for follow up. Consider the following factors when assessing the need for follow-up: Type of exposure Type and amount of fluid/tissue Infection status of source patient Susceptibility of exposed individual Evaluate exposure source. If the source patient is known, test for HBsAg, HCV antibody, and HIV antibody. The use of a rapid HIV antibody test facilitates decisionmaking about the use of PEP within hours of the exposure. For patients who cannot be tested, consider medical diagnoses, clinical symptoms, and history of risk behaviors. If source patient is NOT known, evaluate the likelihood of high-risk exposure. Do not test discarded needles for bloodborne pathogens, as the reliability of these findings is not known. Follow-up. HIV-antibody testing should be repeated at 6 weeks, 3 months, and 6 months post-exposure. Extended follow-up (12-months) is recommended for exposed individuals who become infected with HCV following an exposure to a source co-infected with HIV and HCV. If PEP is given, the exposed individual should be monitored for drug toxicity. CBC, serum creatinine, and LFTs (ALT, AST, bilirubin, and alkaline phosphatase) should be done at baseline (within 72 hours) and at 2 weeks. Exposed individuals should refrain from donating blood, plasma, organs, tissue, or semen. Exposed individuals should be counseled to protect sex- and needle-sharing partners until HIV infection has been ruled out. Harm reduction techniques, including latex barriers during sex and not sharing injection equipment, can be taught during counseling. Patients should also be counseled about the signs and symptoms of acute HIV infection (flu-like syndrome), the need to report it, and to come in for followup testing at the time symptoms appear. Mental health counseling should be offered as needed. Baseline testing. Perform baseline HIV antibody testing, HbsAb, and anti-hcv of the exposed individual as soon as possible after an exposure. If PEP is anticipated, a CBC and LFTs should also be done. PEP management. Start HIV PEP immediately (optimal timeframe is 1-4 hours after exposure). If treatment is delayed more than 36 hours, seek expert consultation. PEP should continue for 28 days, if tolerated, or until source is determined to be uninfected with HIV. Anticipate medication side effects and provide counseling and appropriate symptomatic management. Selection of PEP regimen should include drugs with activity at different stages in the viral replication process. The addition of a third agent should be considered with higher risk exposures; however, with the addition of a third agent comes higher rates of non-completion of the regimen for the full 28-days course. Other considerations include co-morbidities, pregnancy status, medication interactions, tolerability of the drugs, and the possibility of drug resistance. The use of a PI-based regimen should be considered if there is concern for drug resistance (i.e., a treatment-experienced source patient). Treatment decisions should be made based in part on information about the source patient including use of ART and response to therapy (viral load, CD4+ T cell count, current disease state, and any data on HIV resistance testing). Delays in getting information should NOT delay initiation of PEP; modifications can be made at a later date. Expert consultation is strongly encouraged (see PEP resources below). Special considerations. Expert consultation in providing HIV PEP is recommended in the following situations: Delayed exposure report (later than hours) Unknown source (e.g., needle from sharps container) Known or suspected pregnancy of exposed HCP. While most drugs used in HIV therapy have not been found to be a problem in pregnancy, information on the safety of ART in pregnancy is incomplete. Guidelines currently recommend that efavirenz, ddi, and d4t not be used in pregnant women. Consultation with an HIV expert clinician is recommended. Pregnancy does not preclude the use of optimal PEP regimens, nor should PEP be denied solely on the basis of pregnancy. Resistance of the source virus to antiretroviral agents. Resistance testing of the source patient s virus at the time of exposure is not recommended. Selection of drugs to which the source patient s virus is unlikely to be resistant is recommended if the source patient s virus is known or suspected to be resistant to more than one of the drugs considered for the standard PEP regimen. Toxicity of the initial PEP regimen. Adverse symptoms such as diarrhea, nausea, fatigue, and headaches are common with PEP. These can often be managed without changing the PEP regimen by recommending over-the-counter agents or providing prescriptions as needed. Consultation may be needed when side effects are difficult to manage. The use of nevirapine-containing regimen is not currently recommended for post-exposure prophylaxis. 38

47 PEP Resources National Clinicians Post-Exposure Prophylaxis Hotline (PEPline) National HIV Telephone Consultation Service HIV Antiretroviral Pregnancy Registry Food and Drug Administration (FDA): Report unusual or severe toxicity to antiretroviral agents AIDSinfo Non-Occupational Post-Exposure Prophylaxis (npep) Guidelines Non-occupational post-exposure prophylaxis (npep) may be offered after a non-occupational exposure to fluids that are potentially infectious. When an exposure presents a significant risk of transmission, guidelines recommend a 28-day course of ART. If the HIV status of the source is unknown, the guidelines offer no recommendation. Therapy should be initiated as soon as possible, ideally within 72 hours after exposure. Initiation of therapy can be considered for persons who present to care more than 72 hours after the exposure, but the efficacy of prophylaxis is diminished, and must outweigh the risks associated with therapy. Expert consultation is advised. Testing is recommended at baseline, 4-6 weeks, 3 months, and 6 months after exposure. Signs and symptoms of acute seroconversion should be reviewed. Individuals should be counseled about risk-reducing behaviors during the course of npep, as it is not 100% effective in preventing HIV transmission. Multiple studies have shown that approximately 15% of those who present to care requesting npep present again within 12 months. Risk assessment and risk reduction counseling should be performed at each visit. 39

48 Appendix B. Antiretroviral Therapy Generic Name Abbreviation Trade Name abacavir (ABC) Ziagen didanosine (ddi) Videx EC emtricitabine (FTC) Emtriva lamivudine (3TC) Epivir stavudine (d4t) Zerit Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI/NtRTI) Available Dosage Forms 300 mg tablets 20 mg/ml oral solution 125, 200, 250 or 400 mg 200 mg capsule 10 mg/ml oral solution 150, 300 mg tablets 10 mg/ml oral solution 15, 20, 30, and 40 mg capsules 1 mg/ml oral solution Usual Dose* Special Dosing Considerations Adverse Effects 300 mg BID or 600 mg QD Body wt. 60 kg: 400 mg QD With TDF: 250 mg QD Body wt. 60 kg: 250 mg QD With TDF: 200 mg QD 200 mg QD or 240 mg (24 ml) oral solution QD Body wt. > 50 kg: 300 mg QD or 150 mg BID Body wt. < 50 kg: 2 mg/kg BID Body wt. > 60 kg: 40 mg BID Body wt.< 60 kg: 30 mg BID Take with or without food. Alcohol increases abacavir levels 41%; abacavir has no effect on alcohol. Hypersensitivity reaction (may be fatal): signs/symptoms may include rash, fever, nausea, vomiting, malaise, fatigue, loss of appetite, respiratory symptoms (sore throat, cough, shortness of breath). Screening with a genetic test, HLA-B*5701, greatly reduces the risk of this reaction Must take all ddi preparations on an empty stomach, at least 30 minutes before or 2 hours after eating. With TDF, dose may be reduced to 250 mg/day and may be taken with a light meal or snack. Monitor for ddi toxicity. Concomitant use with d4t is not recommended. It may be necessary to separate administration of some medications from ddi dose. Must reduce dose if patient has renal dysfunction. Take with or without food. Must reduce dose if patient has renal dysfunction. Take with or without food. Must reduce dose if patient has renal dysfunction. Take with or without food. Dose reduction may be effective for peripheral neuropathy and is necessary if patient has renal dysfunction. Concomitant use with ddi or AZT not recommended. nausea, body fat changes Serious: lactic acidosis/severe hepatomegaly with steatosis If signs/symptoms of hypersensitivity reaction occur: seek medical evaluation immediately to determine need to discontinue. DO NOT restart: abacavir rechallenge has been associated with fatal hypersensitivity reactions. nausea, vomiting, diarrhea, peripheral neuropathy, headaches, rash Serious: pancreatitis, hepatitis, lactic acidosis with hepatic steatosis, body fat changes headache, diarrhea, nausea, rash, skin discoloration Serious: lactic acidosis with hepatic steatosis, body fat changes nausea Serious: lactic acidosis with hepatic steatosis, body fat changes peripheral neuropathy, nausea Serious: pancreatitis, lactic acidosis with hepatic steatosis (higher incidence than with other NRTIs), hyperlipidemia, body fat changes 40

49 tenofovir (TDF) Viread zidovudine (AZT) Retrovir 300 mg tablet 100 mg capsules, 300 mg tablets, 10 mg/ml IV solution, 10 mg/ml oral solution 1 tablet QD Take with or without food. Must reduce dose if patient has renal dysfunction. Concomitant use with d4t not recommended. 300 mg BID or 200 mg TID Take with or without food. Must reduce dose if patient has renal dysfunction. Concomitant use with d4t not recommended. nausea, diarrhea Serious: vomiting, flatulence, asthenia, renal insufficiency, lactic acidosis with hepatic steatosis nausea, vomiting, headaches, insomnia Serious: anemia, neutropenia, pancreatitis, lactic acidosis with hepatic steatosis, body fat changes *Usual doses are provided. Doses may vary based on weight, the presence of renal or hepatic failure, or when using combinations that have pharmacokinetic interactions. Dose reduction may be required. The association of NRTIs with body fat changes Medications that may have clinically significant drug drug interactions with varies from agent to agent. with NRTIs NRTIs Metabolism of NRTIs AZT - hepatic via AZT - aspirin, cimetidine, cytotoxic drugs, drugs, d4t, d4t, indomethacin, methadone, glucuronidation; renal excretion of metabolites; ddi - probenecid, methadone, ribavirin, probenecid, drugs ribavirin, that interfere drugs with that RBC, interfere WBC; with 55% renal elimination as unchanged drug; d4t - ddi - atazanavir, RBC, WBC dapsone, indinavir (separate doses by at least 2 hours with renal excretion 50%; 3TC - renal elimination; ddi indinavir atazanavir, and ddi dapsone, chewable indinavir tabs), pentamidine, (separate doses drugs by that least cause 2 abacavir - hepatic via alcohol dehydrogenase and pancreatitis/peripheral hours with indinavir neuropathy, and ddi tenofovir, chewable ribavirin; tabs), pentamidine, glucuronyl transferase; metabolites renal excretion d4t - zidovudine, drugs that drugs cause that pancreatitis/peripheral cause peripheral neuropathy/ neuropathy, pancreatitis; tenofovir, 85%; FTC -renal elimination; tenofovir - renal ABC - ethanol; TDF - atazanavir, ddi, lopinavir/ritonavir, cidofovir, ribavirin elimination valganciclovir d4t zidovudine, drugs that cause peripheral neuropathy/ pancreatitis *This list is not all inclusive ABC ethanol TDF atazanavir, ddi, lopinavir/ritonavir, cidofovir, valganciclovir *This list is not all inclusive Generic Name Abbreviation Trade Name atazanavir (ATV) Reyataz darunavir (DRV) Prezista Available Dosage Forms 100,150, 200, 300 mg capsules 400, 600 mg tablets Usual Dose* RTV 100 mg + ATV 300 mg QD 400 mg QD If taken with efavirenz, etravirine, or tenofovir, RTV boosting required 600 mg BID + RTV 100 mg BID - or mg + RTV 100 mg QD (ART-naïve patients only) RTV boosting required Protease Inhibitors (PIs) Special Dosing Considerations Take with a meal or snack. Use with caution with acid-reducing agents: Contraindicated with proton-pump inhibitors. Dose atazanavir 10 hours apart from H2 blocker dosing. Use caution in patients on medications that may cause PR interval prolongation or if underlying conduction defect. Take with food. Use caution if known sulfa allergy. Adverse Effects prolonged PR interval, hyperglycemia, body fat changes, hyperbilirubinemia, possible increased bleeding in pts with hemophilia skin rash, diarrhea, nausea, headache, cold-like symptoms Serious: elevated transaminases, hyperlipidemia, body fat changes, hyperglycemia, erythema multiforme, increased bleeding in pts with hemophilia 41

50 fosamprenavir (FPV) Lexiva indinavir (IDV) Crixivan lopinavir + ritonavir (LPV/r) Kaletra nelvinavir (NFV) Viracept ritonavir (RTV) Norvir saquinavir (SQV) Invirase 700 mg tablet Oral suspension: 50 mg/ml 200, 333, 400 mg capsules LPV 200 mg + RTV 50 and LPV 100 mg + RTV 25 mg tablets LPV 80 mg + RTV 20 mg/1.0 ml oral solution 250, 625 mg tablets 50 mg/g oral powder 100 mg capsules 100 mg. tablets 600 mg/7.5 ml solution 200 mg hard gel capsules, 500 mg tablets ART-naïve patients: 1400 mg BID - or mg + RTV 200 mg QD - or mg + RTV 100 mg BID - or mg + RTV 100 mg QD PI-experienced patients, when QD regimen not recommended: 700 mg + RTV 100 mg BID. With RTV: 800 mg + RTV 100 or 200 mg every 12 hours 2 tablets or 5 ml of oral solution BID - or - 4 tablets QD 1,250 mg BID - or mg TID Used primarily as a booster for other PIs see specific PI Unboosted use not recommended 1000 mg + RTV 100 mg BID Use with caution with any acidreducing agents. Take on empty stomach or with a light meal or a low fat snack. May be taken with food if given with ritonavir. Drink 1.5 liters of water each day. Take with or without food. Does not need to be refrigerated. Take with food. Take with food. Capsules must be refrigerated but may be stored at controlled room temperature for 30 days. Do not refrigerate oral solution. Tablets do not require refrigeration. Take within 2 hours of a meal. diarrhea, nausea, vomiting, headache, rash Serious: hyperlipidemia, body fat changes, transaminase elevation, hyperglycemia, possible increased bleeding in pts with hemophilia nausea, diarrhea, headaches, blurred vision, dizziness, rash Serious: hyperglycemia, body fat changes, increased indirect bilirubin, hyperlipidemia, nephrolithiasis, hemolytic anemia, thrombocytopenia, possible increased bleeding in pts with hemophilia nausea, diarrhea, taste perversion, perioral and circumoral paresthesia Serious: elevated transaminases, hyperglycemia, hyperlipidemia, body fat changes, possible increased bleeding in pts with hemophilia diarrhea, flatulence, nausea, rash Serious: hyperglycemia, body fat changes, hyperlipidemia, elevated transaminases, possible increased bleeding in pts with hemophilia nausea, vomiting, diarrhea, taste perversion Serious: extremity and circumoral paresthesias, elevated transaminases, hyperglycemia, hyperlipidemia, body fat changes, possible increased bleeding in pts with hemophilia nausea, diarrhea, headaches Serious: hyperlipidemia, body fat changes, elevated transaminases, hyperglycemia, possible increased bleeding in pts with hemophilia 42

51 tipranavir (TPV) Aptivus 250 mg capsules 500 mg + RTV 200 mg BID Risk-benefit not yet established in treatmentnaïve patients RTV boosting required Take with food. Use caution if known sulfa allergy. Administer 2 hours apart from ddi-ec and liquid antacids. Review complex drug-drug interactions before using. Use with caution in the setting of hepatic impairment. Refrigerate capsules, may be stored at controlled room temperature (77 F or below) for 60 days. Use caution in patients with increased risk for bleeding or taking medications known to increase risk of bleeding. nausea, vomiting, diarrhea, rash, photosensitivity, increased risk of rash with estrogen use Serious: clinical hepatitis, hepatic decompensation, elevated transaminases, symptoms of sulfa allergy, hyperglycemia, hyperlipidemia, body fat changes, possible increased bleeding in pts with hemophilia Black box warning: TPV has been associated with fatal and nonfatal intracranial hemorrhages The association of PIs with changes in body fat varies from agent to agent. *Usual doses are provided. Doses may vary based on weight, the presence of renal or hepatic failure, or when using combinations that have pharmacokinetic interactions. Metabolism of PIs. All of the PIs are metabolized by the cytochrome P450 enzyme, primarily by the isoenzyme CYP3A4. All PIs inhibit the isoenzyme CYP3A4. The degree of inhibition is dependent on the particular PI being used with ritonavir producing the greatest inhibition of the isoenzyme. Ritonavir induces the isoenzyme CYP1A2 and also inhibits CYP2A6, 2C9, 1A2, 2C19, 2D6, and 2E1. Lopinavir/ritonavir inhibits CYP2D6. Medications that should NOT be administered with PIs: amiodarone, astemizole, bepridil, cisapride, ergotamine derivatives, flecainide, lovastatin, midazolam, pimzide, propafenone, quinidine, rifampin, rifapentine, simvastatin, St. John s Wort, terfenadine, triazolam Medications that have clinically significant drug interactions with PIs Avoid Use or Modify Dosages* atorvastatin, bupropion, carbamezapine, cerivastatin, clarithromycin, clonazepam, cyclosporine, delavirdine, dexamethasone, dihydropyridine calcium channel blockers, diltiazem, disopyramide, dronabinol, efavirenz, ethinyl estradiol, ethosuximide, fluticasone, itraconazole, ketoconazole, lidocaine, meperidine, methadone, metoprolol, mexilitine, nefazadone, nevirapine, perphenazine, phenobarbital, phenytoin, prednisone, propoxyphene, quinine, rapamycin, rifabutin, risperidone, sedative/hypnotics, selective serotonin reuptake inhibitors, sildenafil, stimulants, tacrolimus, tadalafil, theophylline, thioridazine, timolol, tramadol, trazadone, tricyclic antidepressants, verdenafil, verapamil, voriconazole, warfarin *This list is not all inclusive. The presence and the degree of interaction are dependent on the particular PI used. Generic Name Abbreviation Trade Name delavirdine (DLV) Rescriptor etravirine (ETV) Intelence Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Usual Dose* Special Dosing Adverse Effects Considerations Available Dosage Forms 100, 200 mg tablets 100, 200 mg tablets 400 mg 3 times a day; four 100 mg tablets can be dispersed in 3 oz. of water Space doses 1 hour apart from antacids and ddi chewable tablets, suspension, and oral solution. rash, elevated liver enzymes, headaches, fatigue, GI upset, neutropenia Serious: erythema multiforme 200 mg BID Take following a meal. rash, headache, diarrhea, nausea Serious: erythema multiforme 43

52 efavirenz (EFV) Sustiva nevirapine (NVP) Viramune Rilpilverine (RPV) Edurant 50, 100, 200 mg capsules or 600 mg tablets 200 mg tablets 50 mg/5 ml oral suspension (NVP XR is available 400 mg QD) 600 mg QD at or before bedtime 200 mg QD X 14 days (lead-in dosing), 200 mg BID thereafter Not recommended if baseline CD4+ T cell count > 250 cells/mm³ (female) or > 400 cells/mm³ (male) Take on empty stomach as high-fat/high caloric meals increase peak plasma concentrations. Should not be administered during pregnancy or in women with pregnancy potential, unless negative pregnancy test prior to initiation and patient is using 2 effective contraceptive methods, including 1 barrier method. Pregnancy category D. Baseline LFTs and monitor at 2 weeks, 4 weeks, then frequently until 18 weeks of therapy. Continue to monitor LFTs frequently after initial 18-week period. Lead-in dosing should be repeated if drug is interrupted for any reason for > 7 days. 25 mg tablet 25 mg QD Take with food. Space doses several hours apart from antacids or H2-receptor antagonists. rash, drowsiness, diarrhea, dizziness, anxiety, depression, trouble concentrating, unusual dreams (effects usually transient lasting 2-4 weeks), elevated liver enzymes Serious: confusion, encephalopathy rash, GI upset, headaches, elevated liver enzymes Serious: erythema multiforme, hepatotoxicity - lower risk if baseline CD4+ T cell count > 250 cells/mm³ (female) or > 400 cells/mm³ (male) depression, insomnia, headache, rash *Usual doses are provided. Doses may vary based on weight, the presence of renal or hepatic failure, or when using combinations that have pharmacokinetic interactions. NNRTI Metabolism Do NOT administer with Medications with clinically significant interactions avoid use or modify dosages nevirapine delavirdine efavirenz Cytochrome P450 metabolism primarily by CYP2B6 and CYP 3A family; causes induction of CYP3A isoenzymes Cytochrome P450 metabolism primarily by isoenzymes from the CYP3A family although CYP2D6 may play a minor role; causes inhibition of CYP3A and CYP2D6 isoenzymes Cytochrome P450 metabolism primarily by isoenzymes CYP3A4 and CYP 2B6; causes induction of CYP3A4 isoenzymes; causes inhibition of CYP 2C9, 2 C19, and 3A4 isoenzymes rifampin, rifapentine, St. John s Wort alprazolam, amiodarone, astemizole, bepridil, carbamazepine, cisopride, ergotamine derivatives, flecainide, fosamprenavir, H2 blockers, lovastatin, midazolam, phenytoin, phenobarbital, pimozide, propafenone, proton pump inhibitors, rifabutin, rifampin, rifapentine, St. John s Wort, simvastatin, terfenadine, triazolam asemizole, cisopride, ergotamine derivatives, midazolam, rifapentine, St. John s Wort, terfenadine, triazolam, voriconazole ketoconazole, methadone, clarithromycin, oral contraceptives, protease inhibitors, rifabutin, voriconazole amphetamines, amphotericin, antacids, atorvastatin, bupropion, calcium channel blockers, erivastatin, clarithromycin, clonazepam, dapsone, didanosine, dihydropyridines, ethosuximide, ketoconazole, methadone, nefazadone, protease inhibitors, quinidine, sedative/hypnotics, selective serotonin reuptake inhibitors, sildenafil, tadalafil, vardenafil, voriconazole, warfarin carbamezapine, clarithromycin, oral contraceptives, methadone, phenobarbital, phenytoin, pimozide, protease inhibitors, rifabutin, rifampin, voriconazole, warfarin 44

53 etravirine rilpivirine Cytochrome P450 metabolism; causes induction of CYP 3A4 isoenzyme; causes inhibition of CYP2C9 and CYP2C19 Cytochrome P450 primarily with induction of isoenzyme CYP3A carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, rifabutin, St. John s Wort, other NNRTIs, ritonavir-boosted tipranavir, ritonavir-boosted fosamprenavir, ritonavir-boosted atazanavir, full dose ritonavir, non-ritonavir-boosted PIs. other NNRTIs, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, proton pump inhibitors, dexamethasone, St. John s Wort amiodarone, bepridil, clarithromycin, cyclosporine, dexamethasone, diazepam, disopyramide, flecainide, itraconazole, ketoconazole, lidocaine (systemic), lopinavir/ritonavir, maraviroc, mexiletine, propafenone, quinidine, tacrolimus, sirolimus, voriconazole, warfarin; coadministration of etravirine with substrates, inhibitors, or inducers of CYP3A4, CYP2C9, and/or CYP2C19 may alter the therapeutic effect or adverse events profile of etravirine or the co-administered drugs. Use caution with these drugs in patients on etravirine *This list is not all inclusive boosted and unboosted protease inhibitors, antacids, azole fungal agents, H2-receptor antagonists, macrolide antibiotics Generic Name Abbreviation Trade Name Fusion Inhibitor: enfuvirtide (T20) Fuzeon CCR5 Antagonist: maraviroc (MVC) Selzentry Available Dosage Forms 180 mg vials reconstitute with 1.1 ml sterile water (90 mg/ml) 150 and 300 mg tablets Entry Inhibitors Usual Dose Special Dosing Considerations Adverse Effects 90 mg SQ every 12 hours Patients must be willing and able to prepare/administer injections. Requires thorough education about storage, preparation, SQ injection, and prevention of injection site reactions. Reconstituted drug may be refrigerated up to 12 hours prior to use. 150 mg BID when given with strong CYP3A inhibitors (with or without CYP3A inducers) including PIs (except tipranavir/ritonavir) 300 mg BID when given with NRTIs, enfuvirtide, tipranavir/ritonavir, nevirapine, and other drugs that are not strong CYP3A inhibitors 600 mg BID when given with CYP3A inducers, including efavirenz, etravirine, rifampin, etc. (without a CYP3A inhibitor) Take with or without food. Must reduce dose if patient has renal dysfunction. local injection site reactions, diarrhea, nausea, fatigue Serious: hypersensitivity reaction, bacterial pneumonia abdominal pain, cough, dizziness, headache, rash, fever, orthostatic hypotension, musculoskeletal symptoms, upper respiratory infections, hepatotoxicity Metabolism of Entry Inhibitors Enfuvirtide: catabolism to its constituent amino acids with recycling of amino acids in the body pool Maraviroc: cytochrome P450 (CYP3A substrate). Care should be used with administering maraviroc with a CYP3A inducer, as this could lower maraviroc concentrations. Co-administration with a CYP3A inhibitor may raise maraviroc levels. In both cases dose adjustments may be necessary. Medications that have clinically significant drug interactions with maraviroc*: clarithromycin, carbamazepine, delavirdine, efavirenz, intraconazole, ketoconazole, rifampin, phenobarbital, phenytoin, protease inhibitors (except tipranavir/ritonavir), St. John s Wort *This list is not all inclusive 45

54 Generic Name Abbreviation Trade Name raltegravir (RAL) Isentress Available Dosage Forms 400 mg tablets Metabolism: UGT 1a1-mediated glucuronidation Usual Dose Integrase Inhibitor Special Dosing Considerations Adverse Effects 400 mg BID Take with or without food nausea, headache, diarrhea, fever, CPK elevation Trade Name Abbreviation Atripla (FTC/TDF/EFV) Combivir (AZT/3TC) Complera (FTC/RPV/TDF) Epzicom (ABC/3TC) Trizivir (AZT/3TC/ABC) Truvada (FTC/TDF) Available Dosage Forms FTC 200 mg + TDF 300 mg + EFV 600 mg at or before bedtime AZT 300 mg + 3TC 150 mg FTC 200 mg + RPV 25 mg + TDF 300 mg ABC 600 mg + 3TC 300 mg ABC 300 mg + AZT 300 mg + 3TC 150 mg FTC 200 mg + TDF 300 mg Usual Dose 1 tablet QD 1 tablet BID 1 tablet QD 1 tablet QD 1 tablet BID 1 tablet QD Fixed Dose Combinations Special Dosing Considerations Recommend taking on an empty stomach as highfat/high-calorie meals increase peak plasma concentrations. Pregnancy category D: Should not be administered during pregnancy or in women with pregnancy potential, unless negative pregnancy test prior to initiation and patient using one effective contraception method and one barrier method. Take with or without food. Take with food. Take with or without food. Take with or without food. Take with or without food. Adverse Effects See individual components. See individual components. See individual components. Risk of hypersensitivity reaction; see individual components. Risk of hypersensitivity reaction; see individual components. See individual components. 46

55 Appendix C. List of Abbreviations Ab antibody KS Kaposi sarcoma ADAP AIDS Drug Assistance Program LDL low-density lipoprotein Ag antigen LFT liver function tests AIDS acquired immunodeficiency syndrome MAC Mycobacterium avium complex AETC AIDS Education and Training Center MTCT mother-to-child transmission AFB acid-fast bacillus MMR measles, mumps, rubella ALT alanine aminotranferase MRI magnetic resonance imaging ART antiretroviral therapy MSM men who have sex with men AST aspartate aminotransferase MTB Mycobacterium tuberculosis BID 2 times a day NNRTI non-nucleoside reverse transcriptase inhibitor BMD bone mineral density NSAIDS non-steroidal anti-inflammatory drugs BMI body mass index NRTI nucleoside reverse transcriptase inhibitor BUN blood urea nitrogen NtRTI nucleotide reverse transcriptase inhibitor CBC complete blood count npep non-occupational post-exposure prophylaxis CDC Centers for Disease Control and Prevention OHL oral hairy leukoplakia CLIA Clinical Laboratory Improvement Amendment OI opportunistic infection CMV cytomegalovirus PCP Pneumocystis jiroveci pneumonia CNS central nervous system PCR polymerase chain reaction CPK creatinine phosphokinase PEP post-exposure prophylaxis CSF cerebrospinal fluid PI protease inhibitor CT computerized axial tomography PID pelvic inflammatory disease CVD cardiovascular disease PGL persistent generalized lymphadenopathy DHHS Department of Health and Human Services PLWH people living with HIV DNA deoxyribonucleic acid PML progressive multifocal leukoencephalopathy DOT directly observed therapy PPD purified protein derivative skin test for TB; also EIA/ELISA enzyme-linked immunoassay called Mantoux test FDA Food and Drug Administration PTSD post-traumatic stress disorder HAV hepatitis A virus QD 1 time a day HBV hepatitis B virus RNA ribonucleic acid HCV hepatitis C virus SMZ sulfamethoxazole HDL high density lipoprotein SQ subcutaneous HIV human immunodeficiency virus STI sexually transmitted infection HLA human leukocyte antigen TB tuberculosis HPV human papillomavirus TID 3 times a day HSV herpes simplex virus Td tetanus, diphtheria vaccine IgG immunoglobulin G Tdap tetanus, diphtheria, acellular pertussis vaccine IGRA interferon gamma release assay TMP trimethoprim IFA immunofluorescence assay UNAIDS Joint United Nations Programme on HIV/AIDS INH isoniazid VZIG varicella zoster immune globulin IDU injection drug user/injection drug use VZV varicella zoster virus Note. Abbreviations for antiretroviral medications can be found in Appendix B 47

56 Appendix D. National AIDS Services, Hotlines, and On-Line Resources AETC National Resource Center Provides listings of regional AETCs, training materials, clinical resources, and training opportunities. AIDSinfo A service of U.S. DHHS; provides information on HIV treatment, clinical care, and current treatment guidelines HIV-0440 ( ) AIDS InfoNet Provides fact sheets on treatments, prevention, social services, and web resources; easy to print, appropriate for patient and clinician education; updated on a regular basis. Most fact sheets are available in English and Spanish; also other languages. American Academy of HIV Medicine (AAHIVM) Provides education resources and credentialing services. American Foundation for AIDS Research (AmFAR) Provides information about basic science and clinical research and public policy programs. Association of Nurses in AIDS Care (ANAC) Networking, information exchange, social awareness, and advocacy. CDC National Prevention Information Network (NPIN) National reference, referral, and distribution service for HIV, STIs, and TB; access to databases, materials, guidelines, referrals, and training centers for HIV, STIs, and TB HIV Dent Information on oral manifestations of HIV, infection control, PEP protocols, pediatric/adolescent care, medications, large picture gallery, other resources. HIV InSite Sponsored by UCSF. Provides search capabilities in broad science, prevention, and treatment spectrum. Infectious Diseases Society of America (IDSA) Information on practice guidelines, journal publications, conferences, advocacy, public policy, and other resources related to infectious disease. International AIDS Society USA Provides education and information to clinicians who care for PLWH. National Clinicians Post- Exposure Prophylaxis Hotline (PEPline) 24-hour hotline with up-to-date information on managing occupational exposure to blood borne pathogens National HIV/AIDS Telephone Consultation Service (Warmline) National HIV telephone consultation service for providers offering clinical information and individualized consultations from clinicians experienced in HIV care National Minority AIDS Council (NMAC) Programs and services for communitybased organizations serving minorities affected by HIV. Programs include conferences, research, treatment information, and technical assistance. National Native American AIDS Prevention Center (NNAAPC) Information on HIV and related diseases in American Indians, Alaska Natives, and Native Hawaiians. Women, Children, and HIV: Resources for Prevention and Treatment Designed to provide current clinical information and training resources on maternal/child HIV infection. 48

57 Appendix E. National AIDS Services, Hotlines, and On-Line Resources AIDS Drug Assistance Programs (ADAP) are authorized under Title II of the Ryan White Program and administered by HRSA, an agency of the Department of Health and Human Services. States are required to use a portion of their funding to provide medications to treat HIV and manage opportunistic conditions. Qualifications and amount of access varies from state to state; state-specific information can be obtained from the following telephone numbers: Colorado.... (303) Kansas... (785) Nebraska... (402) New Mexico.. (505) North Dakota... (701) South Dakota... (605) Utah. (801) Wyoming. (307) Pharmaceutical companies with medication assistance programs for HIV-infected patients who are unable to afford the cost of their medications are listed below. Eligibility requirements vary from program to program, some assess need on a case-by-case basis and many require the applications for assistance be initiated by a physician. For more information, contact the companies directly. Drug Name Brand Name Manufacturer Telephone ABC + 3TC lamivudine (3TC) zidovudine (AZT, ZDV) abacavir (ABC) AZT + 3 TC AZT + 3TC + ABC Fosamprenavir delavirdine (DLV) nelfinavir (NFV) maraviroc (MVC) Epzicom Epivir Retrovir Ziagen Combivir Trizivir Lexiva Rescriptor Viracept Selzentry ViiV Healthcare Bridges to Access: didanosine (ddi) atazanavir (ATV) efavirenz (EFV) stavudine (d4t) TDF + FTC + EFV saquinavir (SQV) enfuvirtide (T20) nevirapine (NVP) tipranavir (TPV) lopinavir/ritonavir (LPV/r) ritonavir (RTV) darunavir (DRV) etravirine (ETV) rilpivirine (RPV) indinavir (IDV) raltegravir (RAL) tenofovir (TDF) emtricitabine (FTC) TDF + FTC TDF + FTC + EFV FTC + RPV + TDF Videx EC Reyataz Sustiva Zerit Atripla Invirase Fuzeon Viramune Aptivus Kaletra Norvir Prezista Intelence Edurant Crixivan Isentress Viread Emtriva Truvada Atripla Complera Bristol-Myers Squibb Company Roche Boehringer Ingelheim Abbott Laboratories Janssen Pharmaceuticals Merck & Co., Inc Gilead

58 Appendix F. Regional and National AETC Programs REGIONAL CENTERS Delta Region AETC Serving Arkansas, Louisiana, Mississippi New Orleans, Louisiana Florida/Caribbean AETC Serving Florida, Puerto Rico, and the Virgin Islands Tampa, Florida Midwest ATEC Serving Illinois, Indiana, Iowa, Michigan, Minnesota, Missouri, Wisconsin Chicago, Illinois Mountain Plains AETC Serving Colorado, Kansas, Nebraska, New Mexico, North Dakota, South Dakota, Utah, Wyoming Denver, Colorado New England AETC Serving Connecticut, Maine, Massachusetts, New Hampshire, Vermont, Rhode Island Boston, Massachusetts New York/New Jersey AETC Serving New Jersey, New York New York, New York Northwest AETC Serving Alaska, Idaho, Montana, Oregon, Washington Seattle, Washington Pacific AETC Serving Arizona, California, Hawaii, Nevada, and the 6 U.S.-affiliated Pacific jurisdictions San Francisco, California Pennsylvania/Mid-Atlantic AETC Serving Delaware, Maryland, Ohio, Pennsylvania, Virginia, Washington D.C., West Virginia Pittsburgh, Pennsylvania Southeast ATEC Serving Alabama, Georgia, Kentucky, North Carolina, South Carolina, Tennessee Atlanta, Georgia Texas/Oklahoma AETC Serving Texas, Oklahoma Dallas, Texas NATIONAL AND INTERNATIONAL CENTERS National Evaluation Center San Francisco, CA National Resource Center Newark, N.J National Center for HIV Care in Minority Communities Washington, DC, National HIV/AIDS Clinicians Consultation Center San Francisco, CA HIV Medical Consultation: Perinatal Consultation: Post-exposure Consultation: For administrative issues: National Multicultural Center Washington, D.C International Training and Education Center for Health Seattle, WA

59 Appendix G. Mountain Plains AETC Regional Office and Local Performance Sites REGIONAL OFFICE Mountain Plains AETC University of Colorado Denver Anschutz Medical Campus E. 17th Avenue Aurora, CO (p) (303) (f) (303) Lucy Bradley-Springer, PhD, RN, ACRN, FAAN Principal Investigator and Director, MPAETC Associate Professor, Division of Infectious Diseases, School of Medicine (303) Anna Kinder, MS, OTR/L Regional Program Manager (307) Paul Cook, PhD Project Evaluator, MPAETC Assistant Professor, College of Nursing (303) Emma de Anda Sosa Program Assistant, MPAETC (303) LOCAL PERFORMANCE SITES Colorado AETC University of Colorado Denver Anschutz Medical Campus E. 17th Avenue, AO1 Aurora, CO (p) (303) (f) (303) Dakota AETC 1400 W. 22nd Street Sioux Falls, SD (p) (888) (f) (605) Veronica Soler, MD Principal Investigator, Dakota AETC Medical Director, South Dakota Department of Internal Medicine USD School of Medicine Gus Alonto, MD Medical Director, North Dakota Char Lowman, BA Program Coordinator, Dakota AETC Department of Internal Medicine USD School of Medicine (605) Steven Johnson, MD Medical Director, MPAETC Professor of Medicine, Division of Infectious Diseases, School of Medicine Marla Corwin, LCSW, CACIII Clinical Education Coordinator, MPAETC Instructor, Division of Infectious Diseases, School of Medicine (303) Whitney Starr, MS, FNP Clinical Education Coordinator, MPAETC Instructor, Division of Infectious (303) Monica Carten, MD Medical Director, Colorado AETC Assistant Professor, Division of Infectious Diseases, School of Medicine MeriLou Johnson, MSW, MPA Program Director, Colorado AETC Associate Professor, Division of Infectious Diseases, School of Medicine Lisa Lawrence, MSW Program Coordinator, Colorado AETC Anne Grande, BS Education Coordinator, North Dakota, Dakota AETC (p) (701)

60 Kansas AETC University of Kansas, School of Medicine Wichita 1010 North Kansas, #2027 Wichita, KS (f) (316) Donna Sweet, MD Principal Investigator and Director, Kansas AETC Professor of Internal Medicine Susan Tusher, LMSW Senior Coordinator, Kansas AETC (316) New Mexico AETC University of New Mexico School of Medicine Truman Street Clinic 625 Truman Street NE Albuquerque, NM Michelle Iandiorio, MD Principal Investigator (505) Tracy Tessman Education and Outreach Coordinator New Mexico AETC (505) (Mary) Jann DeWitt, PhD Co-Director, Utah AETC Assistant Professor, Department of Family and Preventive Medicine (801) Tiffani Pestotnik, MPH Grant Coordinator, Utah AETC (801) Sara Simonsen, BSN, MSPH Education Coordinator, Utah AETC Research Associate, Department of Family and Preventive Medicine (801) Nebraska AETC University of Nebraska Medical Center Nebraska Medical Center Omaha, NE (p) (866) (f) (402) Susan Swindells, MBBS Director, Nebraska AETC Terry K. Wantanbe Professor Medical Director, HIV Clinic Ann Fitzgerald, APRN Coordinator, Nebraska AETC (402) Deborah Justesen Project Assistant, Nebraska AETC (402) Mark Clark Administrative Assistant NMAETC Utah AETC Division of Infectious Diseases Department of Internal Medicine University of Utah 30 N 1900 E Room 4B319 Salt Lake City, UT (p) (801) (f) (801) Harry Rosado Santos, MD Principal Investigator, Utah AETC Professor of Internal Medicine harry.rosado@hsc.utah.edu C. Maggie Snyder, PA-C Director, Utah AETC Maggie.snyder@hsc.utah.edu (801) Wyoming AETC Casper Natrona County Health Department 851 Werner Court, Suite 292 Casper, WY Mark Dowell, MD, FACP Medical Director, Wyoming AETC Rocky Mountain Infectious Diseases, Casper Anna Kinder, MS, OTR/L Program Director, Wyoming AETC akinder@wyaetc.org (307)

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64 Mountain Plains AIDS Education and Training Center (MPAETC) University of Colorado Denver Anschutz Medical Campus (303)