The face of HIV/AIDS has changed dramatically since. Early Detection and Management of HIV Infection CASE-BASED REVIEW

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1 CASE-BASED REVIEW Early Detection and Management of HIV Infection Case Study and Commentary, Laura Herrera, MD, and Emily J. Erbelding, MD, MPH Abstract Objective: To review an approach to HIV counseling and testing and the selection of highly active antiretroviral therapy (HAART). Methods: Qualitative assessment of the literature. Results: When HIV risk behaviors are identified, patients should be counseled on how the behaviors place them at risk and should be encouraged to undergo HIV testing. The workup of a patient newly diagnosed with HIV infection includes baseline measures of CD4+ cells and HIV viral load, routine chemistry studies, and laboratory parameters to monitor toxicity of antiretroviral therapy (eg, hyperglycemia related to use of protease inhibitors). The ultimate goals of antiretroviral therapy are to improve HIV-related symptoms, to prevent the clinical complications of AIDS, and to reduce mortality. In general, HAART should be considered carefully when the CD4+ cell count is below 350 cells/mm 3 or plasma HIV RNA levels are higher than 55,000 copies/ml. At all follow-up visits, medication adherence should be addressed with specific questions about missed doses. Once HAART is established, attention should be given to detecting signs and symptoms of medication toxicity, and discussion about sexual and drug use behavior should continue. Conclusion: Early detection of those infected with HIV along with early initiation of appropriate HIV care is critical to reducing the overall morbidity and mortality associated with HIV/AIDS in the United States. Multidisciplinary teams may be required to support a high level of medication adherence. INSTRUCTIONS The following article, Early Detection and Management of HIV Infection, is a continuing medical education (CME) article. To earn credit, read the article and complete the CME evaluation form on page 511. OBJECTIVES After participating in the continuing education activity, primary care physicians should be able to: 1. Identify patients engaged in behaviors that place them at high risk for acquiring HIV infection 2. Adequately counsel and test high-risk patients for HIV infection 3. Be able to identify the drug classes that may be components of highly active antiretroviral therapy 4. Be able to identify issues underlying poor medication adherence that may impact on long-term success of therapy The face of HIV/AIDS has changed dramatically since the first case descriptions of AIDS were reported in Following the introduction of highly active antiretroviral therapy (HAART) in 1995, there were initially dramatic reductions in AIDS-related mortality [1]. However, since 1998 the death rate from AIDS has held steady at approximately 16,000 per year, while incident cases of HIV have also remained steady at approximately 40,000 per year [2]. The mortality rate has decreased more than the estimated HIV incidence rate, suggesting that the population of persons living with HIV is growing in the United States. The promise of a longer and better quality of life for those diagnosed with HIV infection has led to decreased fears of contracting the virus, which in turn may be related to the recent increase of high-risk sexual behaviors as indicated by the emergence of syphilis epidemics among men who have sex with men [3]. A rising proportion of syphilis cases are also HIV-infected [3], suggesting an urgent need to improve our ability to identify persons infected with HIV and to improve HIV prevention services provided to them. This article discusses an approach to HIV counseling and testing as well as considerations around initiation of antiretroviral therapy in patients with newly diagnosed HIV infection or newly initiating therapy. Measures for supporting medication adherence and integrating prevention efforts into HIV clinical care are also presented. From the Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD. Vol. 10, No. 9 September 2003 JCOM 503

2 MANAGEMENT OF HIV INFECTION Table 1. Groups at Risk for HIV Infection High risk Persons with sexually transmitted diseases Injection drug users Men who have sex with men Regular sexual partner of a high-risk individual Increased risk Persons who consider themselves at risk Pregnant women Persons with fever or illness of unknown origin Persons with an opportunistic infection, including active tuberculosis Persons who live in high prevalence areas (> 1%) Data from Centers for Disease Control and Prevention. Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep 2001;50(RR-19):1 57. CASE STUDY Initial Presentation A 23-year-old man presents to his primary care physician because he has been experiencing a burning sensation with urination for the past 2 days. History The patient denies any associated fevers, hematuria, or flank pain. He has been tolerating oral intake well without nausea, vomiting, or diarrhea. He has no significant past medical history. He takes no medications and has no allergies to medications. He reports that he has had 1 steady male sex partner for the past year with whom he does not use condoms. He also has 2 other new male partners with whom he has had sexual contact over the past month and with whom he uses condoms 100% of the time with rectal penetration, but inconsistently with oral-genital contact. He reports using drugs and alcohol socially, sometimes getting high or drunk to be more successful in meeting new sex partners, but denies a history of injection drug use. He denies any previous history of sexually transmitted diseases and has never been tested for HIV infection. Should this patient be tested for HIV infection? The case patient has several risk factors for acquiring HIV (Table 1). First, he is a young gay man. Though heterosexual men and women are also at risk for HIV exposure, it is estimated that nearly half of all newly diagnosed males with HIV are men who have sex with men [2]. The patient also reports sexual encounters without the use of a condom in the context of drug-using social networks. Last, he has symptoms of what may be a sexually transmitted disease. This patient should be counseled on his current risky behaviors and how they put him at risk, and he should be encouraged to accept HIV testing. In recommending testing, the physician should assure the patient that his confidentiality will be protected. Informed written consent should be obtained prior to testing if this is required by local law. HIV testing sites that receive federal funding must perform risk reduction counseling for patients who seek testing according to federal standards [4]. Private providers who order HIV tests should consider these guidelines as a measure of best practice: counseling should include patient education on the modes of transmission of HIV as well as a discussion of personal behaviors that put the patient at risk for acquiring HIV. Ideally, the counseling session should lead to an individualized plan with concrete and achievable action items for reducing risk behavior. Finally, the patient should be told that the results of an HIV test might be negative if exposure and infection occurred very recently, and that, for a particular recent exposure of concern, repeat testing within 3 to 6 months may be recommended. Physical Examination and HIV Testing On physical examination, the patient is uncircumcised. There are no ulcers or other lesions present. Examination of the urethra reveals mucopurulent discharge, and a specimen of the urethral swab material is sent for diagnostic tests for gonorrhea and chlamydia. Microscopic examination of the Gram-stained urethral discharge is consistent with gonorrhea. The patient is treated with 1 dose of ciprofloxacin 500 mg as well as doxycycline 100 mg twice daily for 7 days. The patient agrees to undergo confidential HIV testing. The results of HIV serologic testing are returned 1 week later: enzyme immunoassay is reactive and the Western blot result is indeterminate (specific binding demonstrated to the p24 protein). Is this patient infected with HIV? In the setting of the case patient s recent risk behaviors and diagnosis of a sexually transmitted disease, an indeterminate HIV serologic result is very concerning for early indication of HIV infection. A Western blot test is the standard reflex test performed following a reactive HIV enzyme immunoassay test. The result is considered indeterminate if there is any binding demonstrated to any protein band on the blot corresponding to either HIV core, polymerase, or envelope proteins. A positive HIV Western blot must have reactivity to 2 of 3 bands at p24, gp41 or gp120/160, while a negative HIV 504 JCOM September 2003 Vol. 10, No. 9

3 CASE-BASED REVIEW Western blot has no bands present. A patient with an indeterminate HIV Western blot should be evaluated clinically for signs or symptoms of acute retroviral syndrome or primary HIV infection (Table 2) [5]. Either asymptomatic HIV seroconversion or acute retroviral syndrome can be confirmed by follow-up HIV serology testing that shows new antibodies directed against HIV or by laboratory evidence of HIV viral components: HIV ribonucleic acid [RNA] or p24 antigen. P24 antigen testing should be used with caution because its sensitivity can be as low as 77% depending on the time between onset of symptoms and screening [6]. In addition, during seroconversion there are extremely high levels of HIV in the circulation more than 10 6 copies/ml in many cases as compared with between 10 3 and 10 5 copies/ml during chronic infection [7] which suggests that the person undergoing seroconversion may be highly infectious to sex and needlesharing contacts. Therefore, it is important to perform prevention counseling when evaluating patients who may have recently acquired HIV and are undergoing seroconversion. Patient Follow-up The patient cannot be located for follow-up despite multiple attempts to reach him. After 3 years, he returns to the physician s office. He states that he had HIV testing through a health department testing site following the indeterminate Western blot result. This test was positive, but he could not deal with the diagnosis so he put it out of his mind. For the past month, he has noticed that he tires with minimal exertion and has 3 or 4 loose bowel movements per day. He has lost 15 lb since his last visit 3 years ago and has thrush evident on oral examination. How should this patient be counseled? What other evaluations should be performed at this time? When providing care for the person with newly diagnosed HIV infection, or for those with established HIV infection and newly initiating care, it is important to review the modes of HIV transmission, instruct the patient on correct condom use, and emphasize the importance of disclosure of HIV status to sexual partners. In most local health departments, disease intervention specialists will confidentially notify sex and needle-sharing partners of those identified with HIV infection so that these partners can take measures to protect their own health. The physician should also discuss with the HIV-infected patient the laboratory measures that are used to stage HIV infection and measure immunologic status, including the CD4+ cell count and HIV viral load. Patients Table 2. Signs and Symptoms of Primary HIV Infection Fevers Adenopathy Pharyngitis Rash Myalgias Diarrhea Headache Nausea and vomiting Hepatosplenomegaly Weight loss Thrush Neurologic symptoms should be told that while HIV is a treatable illness that can be managed with lifelong therapy, it cannot be cured. The standard evaluation for a patient newly initiating HIV care should focus on past medical history, surgical history, hospitalizations, medications (including over-thecounter medications), the use of herbal or dietary supplements, and any known drug allergies. Immunization history should also be recorded. Social history should include an assessment of sexual behavior risks and review of past and current drug use, including a discussion of the use of steroids for fitness enhancement, street drugs, club drugs, and alcohol use. The information gathered through the social history may help to identify the patient s HIV transmission category if that was not previously known so that any behavior risks for transmitting HIV to others can be more effectively addressed in ongoing clinical care. A review of systems should specifically target symptoms that might be attributable to HIV infection itself or to its complications. These include constitutional symptoms of fever, chills, sweats, and weight loss; respiratory symptoms of cough or shortness of breath; nausea, vomiting, diarrhea, abdominal pain, dysphagia, and odynophagia; rashes or pruritus; and headaches, changes in vision, paresthesias, and weakness. Manifestations of psychiatric syndromes, especially low mood, sadness, and hopelessness, should also be explored. A complete physical examination should be performed, with special attention to adenopathy (a nonspecific sign suggesting HIV), the presence of oropharyngeal lesions such as thrush or oral hairy leukoplakia, evaluation of the abdomen for tenderness or hepatosplenomegaly, a thorough skin evaluation, a complete genitourinary examination to rule out any asymptomatic sexually transmitted diseases, and a neurologic examination to assess for symptoms of peripheral neuropathy and rule out any cognitive deficits. At the initial visit, baseline laboratory evaluation should include a complete blood count with platelets, CD4+ Vol. 10, No. 9 September 2003 JCOM 505

4 MANAGEMENT OF HIV INFECTION Table 3. Baseline Laboratory Tests for Newly Diagnosed HIV Infection Complete blood count with platelets Chemistry profile, including serum transaminases CD4+ T lymphocyte count Plasma HIV ribonucleic acid measurement Lipid profile RPR test or VDRL test for syphilis Hepatitis virus serology Toxoplasma immunoglobulin G serology RPR = rapid plasma reagin; VDRL = Venereal Disease Research Laboratory. lymphocyte subset testing, measurement of HIV viral load, and routine serum chemistry studies. The CD4+ cell count documents the current level of immunocompromise, while measurement of the HIV viral load quantifies the level of viremia, which independently predicts the rate of clinical progression to symptomatic AIDS [7]. Anemia is a common laboratory abnormality found in HIV-infected patients, and its course in these patients is usually multifactorial. It may be due to an effect of HIV infection that results in the suppression of hematopoietic progenitor cells [8] or may result from use of medications such as azidothymidine or from nutritional deficiencies. In addition, 8% of HIV-infected patients and up to 30% of patients with AIDS will have thrombocytopenia [9]. Perhaps the most common and important serum chemistry abnormality is elevated liver-associated enzymes. Up to 50% of HIV-infected patients are coinfected with a hepatitis virus, most commonly hepatitis C. The presence of hepatitis coinfection may increase the hepatotoxicity of HAART [10]. Other common abnormal chemistry measures, such as low serum albumin, may suggest poor nutritional status, particularly if advanced AIDS is clinically present. It is important to establish other baseline laboratory parameters in order to monitor toxicity of antiretroviral therapy; for example, hyperglycemia may occur in patients who are taking protease inhibitors due to insulin resistance and impaired cellular glucose uptake. Fasting lipids should be measured to evaluate for dyslipidemias that might occur due to HIV infection and/or with HIV treatment. A serologic test for syphilis should be performed. Persons with HIV are frequently coinfected with syphilis, and a new diagnosis of syphilis may be a marker for continued risky sexual encounters that may transmit HIV to others. Hepatitis serology (hepatitis C virus antibody, antibody to hepatitis B core antigen, hepatitis B surface antigen, antibody to HBsAg) should be performed to evaluate for underlying liver disease and to determine the need for immunization. Finally, the patient should be tested for immunoglobulin G antibodies to Toxoplasma gondii to assess for prior exposure and define need for prophylaxis (Table 3). Laboratory Testing The patient returns to find out the results of his tests. His CD4+ cell count is 242 cells/mm 3 and his viral load is 72,000 copies/ml. The remainder of the test results are within normal limits. Should the physician advise this patient to initiate HAART? The ultimate goals of antiretroviral therapy are to improve HIV-related symptoms, to prevent the clinical complications of AIDS, and to reduce mortality. These potential benefits must be weighed against possible toxicity of therapy. The case patient is experiencing HIV-related symptoms (fatigue, diarrhea, thrush), and he will likely feel better and his risk of serious clinical illness will decrease if he can successfully adhere to and tolerate HAART. Therefore, therapy should be recommended. It is more difficult to determine when the risk-benefit ratio favors starting HAART in an asymptomatic patient. Consensus panel guidelines provide firm support for starting therapy when the CD4+ cell count declines to less than 200/mm 3 ; however, at what point the risk-benefit ratio of initiation of therapy is optimized in asymptomatic patients with CD4+ cell counts over 200/mm 3 remains controversial [11]. In general, HAART should be considered carefully when the CD4+ cell count is below 350 cells/mm 3 or plasma HIV RNAlevels are higher than 55,000 copies/ml [11]. In addition, when deciding whether to recommend HAART, the physician should consider the patient s willingness and readiness to begin therapy, the degree of immunodeficiency, the potential risks and benefits associated with treatment, and the likelihood of adherence. Several factors will affect the patient s willingness and readiness. What are the patient s preconceived ideas about HAART? Is substance abuse an active problem? Does the patient have stable housing? Does the patient have any documented mental illness or undetected depression that might impact negatively on motivation? What kind of social network does the patient have to support medication adherence? These will impact not only upon willingness to start a regimen but also ability to adhere to that regimen. For patients who have symptomatic AIDS, it is essential to provide intensive psychosocial support to quickly address any significant barriers to adherence such as untreated mental illness and ongoing substance abuse in order to improve the chance of a patient receiving the benefits of HAART [12]. Programs designed to provide structured support for medication adherence, such as directly observed HAART linked to methadone maintenance therapy, may be lifesaving [13]. Physicians should discuss with all patients the benefits 506 JCOM September 2003 Vol. 10, No. 9

5 CASE-BASED REVIEW Table 4. Recommended HAART Starting Regimens Regimen Advantages Disadvantages 2 nucleosides and 1 PI 2 nucleosides and 1 NNRTI 3 nucleosides (alternative to NNRTIand PI-based regimens [11]) Durability (especially boosted PIs) Genetic barrier to resistance Spare PIs Central nervous system penetration Decrease in pill burden Spare NNRTIs and PIs Simplicity Metabolic toxicities Gastrointestinal intolerance Increase in pill burden Food requirements Cross resistance among NNRTI class Low genetic barrier to resistance with NNRTI class Less durability Increase in mitochondrial toxicity Hypersensitivity reaction (if abacavir is component of regimen) NNRTI = nucleotide/nucleoside reverse transcriptase inhibitors; PI = protease inhibitor. (Adapted from Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Available at nih.gov/guidelines/default_db2.asp?id=50. Accessed 4 Aug 2003.) and risks associated with immediately initiating therapy versus delaying therapy as they apply to the individual patient. Benefits of therapy for the case patient include improvement of his HIV-related symptoms, immune system maintenance, and prevention of further immune system damage [11]. A possible public health benefit of effective HAART is a decreased risk of a patient transmitting HIV to others. Risks of therapy include drug toxicities, manageable side effects, and decrease in quality of life related to those side effects. There is also the possibility that while the virus is under selection pressure of antiretrovirals and complete viral suppression is not obtained, the evolution of resistant HIV can emerge. This potential pitfall is more likely to occur for patients who only partially adhere to their regimen. The presence of drug-resistant virus will limit future therapeutic options. The potential risks of delaying therapy include the possibility of further clinical complications of HIV related to immune system depletion as well as greater difficulty suppressing viral replication once therapy is initiated. As therapy is delayed, viral diversity will have time to evolve, which may include mutations associated with drug resistance [11]. When choosing a HAART regimen, the physician should consider a number of issues that can impact adherence, including pill burden, simplicity in dosing, how the dosing schedule might fit into a patient s daily routine with respect to timing of meals (some medications need to be taken with food and some on an empty stomach), and potential drug interactions with other prescribed medications. Because performing a thorough assessment to explore some of these issues may take a significant amount of time, other members of the health care team, such as specialized nurse educators or pharmacists, can assist with this task in the busy practice setting [14]. To improve the chances of good medication adherence, the patient should be familiar with the support services available from the clinic and the means of contacting them; they should feel that the clinician and support staff will be available if unanticipated side effects or other issues arise. What are the options when initiating HAART? Available options for initial combination therapy along with general pros and cons of each type of combination are summarized in Table 4. Tables 5, 6, and 7 summarize specific medications, dosing intervals, and food considerations for each specific drug. While it may appear that there is a great number of possible HAART combinations to switch to should the initial regimen fail, resistance to a single drug within the class may confer class-wide resistance. Classwide resistance may severely limit chances of virologic control with salvage regimens that might be considered in the future. Food requirements with the regimen should be considered and discussed with patients initiating a HAART regimen. Certain medications must be taken with food and others on an empty stomach. A written schedule documenting the times the patient is expected to take his or her medicines is often helpful in planning. The patient is able to see how and when the medicines will fit in his or her workday and meal times. Once-daily and twice-daily dosing have become easier with the advent of boosted protease inhibitors and extended-release nucleosides/nucleotides. It may be helpful to the patient if a close family member or friend is involved Vol. 10, No. 9 September 2003 JCOM 507

6 MANAGEMENT OF HIV INFECTION Table 5. Nucleotide/Nucleoside Reverse Transcriptase Inhibitors Drug Dosing Administration Food Restrictions Tenofovir (Viread) 300 mg 1 pill daily Take with a meal Didanosine (Videx EC) 400 mg 1 pill daily Empty stomach Didanosine (Videx) 100 mg or 200 mg 2 pills twice daily or 2 pills Empty stomach once daily Zidovudine (Retrovir) 300 mg 1 pill twice daily No food restrictions Lamivudine (Epivir) 300 mg 1 pill daily No food restrictions Lamivudine (Epivir) 150 mg 1 pill twice daily No food restrictions Emtricitabine (Emtriva) 200 mg 1 pill daily No food restrictions Abacavir (Ziagen) 300 mg 1 pill twice daily No food restrictions Stavudine (Zerit) 40 mg 1 pill twice daily No food restrictions Zalcitabine (Hivid) 0.75 mg 1 pill 3 times daily No food restrictions Zidovudine/lamivudine (Combivir) 1 pill twice daily No food restrictions Zidovudine/lamivudine/abacavir (Trizivir) 1 pill twice daily No food restrictions Table 6. Non-Nucleoside Reverse Transcriptase Inhibitors Food Drug Dosing Administration Restrictions Efavirenz 600 mg 1 pill every night Empty stomach (Sustiva) Nevirapine 200 mg 1 pill daily x 14 days, No food restric- (Viramune) then 1 pill twice tions daily Delavirdine 200 mg 2 pills 3 times daily No food restric- (Rescriptor) tions Initiation of Therapy The patient denies a history of drug use. He reports that he has been feeling down, although he is sleeping well and eating well. He denies a previous history of depression. He has informed his family of his diagnosis, and they support his decision to begin HAART. A combination of zidovudine/lamivudine and efavirenz is chosen because it is a relatively simple regimen and is well tolerated with a high rate of durable viral suppression in clinical trials [11]. The patient is asked to make a return appointment for 2 weeks, primarily to discuss adherence and side effect management. in the medication teaching process so that they can support the patient in maintaining adherence [15]. For the patient starting HAART, it is also helpful to provide anticipatory guidance on managing expected side effects of antiretroviral medication (eg, loperamide for diarrhea related to protease inhibitors). What are the goals of HAART? The long-term goal of HAART is to prevent the clinical complications of HIV/AIDS. Meeting this goal requires restoration of the immune system, as evidenced by an increase in the absolute CD4+ cell count; this outcome is best accomplished by durable virologic suppression. Thus, the more immediate goal for all patients starting HAART who are treatment-naïive is achievement of a viral load below 400 copies/ml by 12 weeks and below 50 copies/ml at 16 to 24 weeks [16]. What issues should be addressed at follow-up visits? In early follow-up visits, it is important to focus on medication adherence [14]. To obtain accurate information on adherence, it is best to be as specific as possible when asking the patient about missed doses: How many pills have you missed in the past 3 days? and How many doses have you missed since your last office visit? Initially acknowledging that perfect adherence is difficult, thereby giving permission to the patient to reveal adherence difficulties, may improve the accuracy of patient reporting [14]: It is common for my patients to sometimes forget to take their medicine. Have you ever experienced that problem? Patients will often report missing pills for various reasons, including forgetfulness, not feeling well, and leaving their medication at home when they leave the house. Although a report of 100% adherence may not be indicative of the number of doses patients have taken, a report of nonadherence tends to be accurate and is a strong predictor of incomplete viral suppression [17]. 508 JCOM September 2003 Vol. 10, No. 9

7 CASE-BASED REVIEW Table 7. Protease Inhibitors and Fusion Inhibitor Drug Dosing Administration Food Restrictions Ritonavir (Norvir) 100 mg 6 pills twice daily Take with food Amprenavir (Agenerase) 150 mg 8 pills twice daily With or without food, avoid high-fat meals Lopinavir/Ritonavir (Kaletra) 133.3/33.3 mg 3 pills twice daily Take with food Nelfinavir (Viracept) 250 mg 3 pills 3 times daily or 5 pills twice daily Take with food Indinavir (Crixivan)* 400 mg 2 pills twice daily Empty stomach Saquinavir soft gel (Fortovase) 200 mg 6 pills 3 times daily Take with food Saquinavir (Invirase) 200 mg 3 pills 3 times daily Take with food Atazanavir (Reyataz) 200 mg 2 pills daily Take with food Enfuvirtide (Fuzeon) 090 mg SQ injection twice daily *May be boosted with ritonavir 800 mg/100 mg twice daily. May be boosted with ritonavir 1600 mg/100 mg once daily. May be boosted with ritonavir 300 mg/100 mg once daily. In later follow-up visits, the focus on medication adherence should continue, and the patient should have a directed examination with specific attention to signs and symptoms of medication toxicity. The patient s overall appearance should be assessed for signs of lipoatrophy or lipodystrophy. Evaluation should also include an assessment of the skin for rashes, the abdomen for any signs of hepatitis or pancreatitis and sensory testing, and reflexes for signs of peripheral neuropathy. Continued discussion about sexual and drug use behavior is also warranted. The laboratory results should be reviewed with the patient. Patients are often encouraged by a documented decrease in HIV viral load that is evident in a 4-week interval of time as well as by the increase in CD4+ cell count that occurs later. These lab indicators often serve as positive feedback that may reinforce good adherence. Adherence should be reviewed at the first visit and at every visit thereafter. Abundant data demonstrate that the higher the rate of adherence, the lower the likelihood of virologic failure. In one study, patients with approximately 95% adherence to a protease inhibitor based regimen ( 3 missed doses per month) had a success rate of almost 80% in obtaining complete virologic suppression [12]. The recent availability of once-daily regimens may be associated with even greater treatment success. The physician should review the patient s medication schedule with him and with any family members involved in his care. During future visits, any indicators of early depression should be discussed as depressed mood may have a significant impact on adherence. Finally, continued discussion and counseling of transmission behaviors in HIV clinical practice remains important for preventing a patient from transmitting HIV to others. Because sexual exposure to drugresistant HIV has been associated with loss of virologic control in persons already HIV infected [15], unprotected sexual encounters or shared injection equipment may pose significant risk to the health of the HIV-infected person as well as to the community. 4 Weeks Later 4 weeks after beginning therapy, the patient reports that he has not missed taking any pills since his last visit. Other than an initial feeling of spaciness attributable to efavirenz that eventually resolved, he denies any side effects. He reports that he has not had any sexual activity or used drugs and alcohol since his last visit. Physical examination is unremarkable, and the physician orders a complete blood count along with CD4+ subset testing, HIV viral load, and a basic serum chemistry panel. The results indicate that his CD4+ cell count is essentially the same, and his HIV viral load is now 2710 copies/ml. Other laboratory test results are within normal limits. Conclusion Early identification of HIV infection in the clinical practice setting may be lifesaving for those with undetected infection. Early detection along with effective initiation of HIV care are critical elements in addressing the HIV/AIDS epidemic in the United States. An individual s successful adherence to HAART will be the most important predictor of a durable response to this therapy. Ongoing multidisciplinary support for both medication adherence and risk behavior reduction is often required to improve clinical outcomes for patients with HIV/AIDS. Corresponding author: Dr. Emily J. Erbelding, 1830 E. Monument St., Rm 445, Baltimore, MD, 21287, eerbeldi@jhmi.edu. Financial disclosures: None. Vol. 10, No. 9 September 2003 JCOM 509

8 MANAGEMENT OF HIV INFECTION Author contributions: conception and design, EJE; drafting of the article, LH; critical revision of the article, LH, EJE. References 1. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Eng J Med 1998;338: Advancing HIV prevention: new strategies for a changing epidemic United States, MMWR Morb Mortal Wkly Rep 2003;52: Primary and secondary syphilis among men who have sex with men New York City, MMWR Morb Mortal Wkly Rep 2002;51: Centers for Disease Control and Prevention. Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep 2001;50(RR-19): Schacker T, Collier AC, Hughes J, et al. Clinical and epidemiologic features of primary HIV infection [published erratum in Ann Intern Med 1997;126:174]. Ann Intern Med 1996;125: Pilcher CD, Wohl DA, Hicks CB. Diagnosing primary HIV infection. Ann Intern Med 2002;136: Lyles CM, Dorrucci M, Vlahov D, et al. Longitudinal human immunodeficiency virus type 1 load in the Italian seroconversion study: correlates and temporal trends of virus load. J Infect Dis. 1999;180: Huang SS, Barbour JD, Deeks SG, et al. Reversal of human immunodeficiency virus type 1-associated hematosuppression by effective antiretroviral therapy. Clin Infect Dis 2000; 30: Sloand EM, Kelin HG, Banks SM, et al. Epidemiology of thrombocytopenia in HIV infection. Eur J Haematol 1992;48: Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Elevated liver enzymes following initiation of antiretroviral therapy. JAMA 2000;283: Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Available at guidelines/default_db2.asp?id=50. Accessed 4 Aug Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000;133: Lucas GM, Flexner CW, Moore RD. Directly administered antiretroviral therapy in the treatment of HIV infection: benefit or burden? AIDS Patient Care STDs 2002;16: Stone VE. Strategies for optimizing adherence to highly active antiretroviral therapy: lessons from research and clinical practice. Clin Infect Dis 2001;33: Hecht FM, Grant RM, Petropoulous CJ, et al. Sexual transmission of an HIV-1 variant resistant to multiple reversetransciptase and protease inhibitors. N Eng J Med 1998;339: Bartlett JG, Gallant JE Medical management of HIV infection Edition ed. Baltimore: Johns Hopkins University, Department of Infectious Diseases, Paterson DL, Potoski B, Capitano B. Measurement of adherence to antiretroviral medications. J Acquir Immune Defic Syndr 2002;31(Suppl 3):S Copyright 2003 by Turner White Communications Inc., Wayne, PA. All rights reserved. 510 JCOM September 2003 Vol. 10, No. 9

9 JCOM CME EVALUATION FORM: Early Detection and Management of HIV Infection To receive 1 hour of AMA PRA Category 1 CME credit, read the article named above and mark your responses on this form. You must complete all parts to receive credit. Then return this form using the fax number or address appearing at the bottom of this page. A certificate awarding 1 hour of category 1 CME credit will be sent to you by fax or mail. This CME Evaluation Form must be fax marked or postmarked within 1 year of this JCOM issue date. Please allow up to 4 weeks for your certificate to arrive. Part 1. Please respond to each statement. Strongly Agree Strongly Disagree I was provided with new information pertinent to my practice. I reaffirmed a specific skill or knowledge. This article will help with clinical decision making. Relevant clinical outcomes are addressed. The case is communicated in a manner that kept my interest. The case presentation is realistic and effective. I could easily interpret the tables and figures. My attitude about this topic changed in some way. Additional comments: Part 2. Please complete the following sentence. As a result of reading this case study, I... see no need to change my practice. will seek more information before modifying my practice. intend to change the following aspect(s) of my practice: (Briefly describe) Part 3. Statement of completion: I attest to having completed the CME activity. Signature: Date: Part 4. Identifying information: Please PRINT legibly or type the following: Name: Fax number Address: Telephone number Social Security number: (Required and confidential) Medical specialty: SEND THE COMPLETED CME EVALUATION FORM TO: BY FAX: BY MAIL: Wayne State University Division of CME 101 Alexandrine, Lower Level Detroit, MI Wayne State University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Wayne State University School of Medicine designates this CME activity for a maximum of 1 hour of category 1 credit toward the Physician s Recognition Award of the American Medical Association. Physicians should claim only those hours of credit actually spent in the educational activity. Vol. 10, No. 9 September 2003 JCOM 511