Question 1. Question 2. HIV OVERVIEW AND UPDATE 2013: What We Need Know. Presenter: Alan Keating Conyers, GA 3/2/2014

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1 HIV OVERVIEW AND UPDATE 2013: What We Need Know Presenter: Alan Keating Conyers, GA Question 1 What geographic region has the highest rate per capita of HIV infection? 1. South America 2. South East Asia 3. Southern Russia 4. Sub-Saharan Saharan Africa Question 2 By 2015, IOM estimates that the percentage of US HIV patients over 50 will be? 1. 45% 2. 50% 3. 55% 4. 60% 1

2 Objectives Provide a brief history of HIV/AIDS disease. Explore the societal and personal impact of HIV/AIDS world wide and nationally. Review the past and present risk factors for HIV and projected future disease trends. Understand the morbidity, co-morbidities, and mortality of HIV/AIDS. Review the current and future treatment protocol s for HIV/AIDS. When did it all begin? Early Years Fears and Myths AIDS patients were all gay or drug users. HIV/AIDS spreads like a wildfire. If you got HIV/AIDS, you would die. You could get AIDS by: Sitting next to someone Touching, hugging, or kissing Drinking from same glass or water fountain Swimming in the same pool Sitting on public toilet seats Being bitten by mosquitoes 2

3 The Truth Roughly 16% of men and 78% of women become HIV-positive through heterosexual contact. HIV infects infants, teens, seniors, and all race groups. Early on in the disease epidemic the death rate was high. Now, antiretroviral drugs allow HIV-positive people to live much longer. No evidence has shown that HIV is spread through touch, casual contact, tears, sweat, saliva, or mosquito bites. Losing Battle Acquired Immunodeficiency Syndrome (AIDS) was first diagnosed on April 24, 1980 with a patient suffering with Kaposi s Sarcoma and Cryptococcus. Initially there were only a handful of cases, with the first cluster of cases reported June 5, By mid 1984, the number diagnosed AIDS cases had risen to about 8,000 individuals with a death toll of roughly 4,500. Breakthrough Researchers isolated the Human Immunodeficiency Syndrome virus (HIV), and it was officially labeled in By the late 1980 s multiple medications and treatment schedules or Cocktails were becoming standard practice. Since combination therapy became available to U.S. HIV patients in 1996, life expectancies have risen exponentially. They are living longer and healthier lives. 3

4 Progress What s the financial impact? National In 2002, the estimated total cost of all new HIV infections in the United States is at $36.4 $ billion. $6.7 billion in direct medical costs. $29.7 billion in productivity losses. Productivity losses are disproportionately borne by minority races/ethnicities. In 2006, the estimated cost of treatment for new HIV patients in the United States was projected to be $12.1 billion annually. 4

5 Personal Medications comprises more than 70 percent of the expense of HIV treatment (2006). It has been estimated that, from the onset of care until death, individual treatment costs averages $2,100 per month. Total lifetime medical cost for U.S. patients infected with HIV was projected to be $618,900 in Who s at risk? Original Risk Factors MSM Activity I.V. Drug Use Haitian Nationality Hemophilia Blood Transfusion recipients Infants 5

6 Current Risk Factors MSM activity Unprotected anal sex is riskier than unprotected vaginal sex. Among MSM participants, unprotected receptive anal sex is riskier than unprotected insertive anal sex. Unprotected sexual intercourse However, the yearly rate of infection is only 8 percent for all heterosexual partners of HIV carriers. I.V. drug use Infants 540,000 children were estimated to have been infected. Adults over 50 By 2015, IOM estimates 50% of US HIV pts. will be over 50. Health care providers Mode of Transmission New HIV infections by mode of transmission (2009) Transmission Risk HIV-1 1 plasma viral load (VL) is the most important factor in predicting transmission the virus. When plasma HIV-1 1 VL is below 1,500 the risk of transmission is considered low. The CDC estimated that there was a 5% transmission rate for those living with HIV infection to others in the U.S. (2006). Therefore, the majority, roughly 95%, of HIV infected individuals did not transmit the virus. This is an 89% decline in the rate since its peak rate in the mid-1980s. 6

7 What s the big picture? Morbidity and Mortally Morbidity - Global Sub-Saharan Saharan Africa is home to almost 65% (24.5 million) of all HIV/AIDS infected individuals, but only 10-11% 11% of the world s total population (2005). It also houses 87% of all the infected children. In this region, women represent more than half (59%) of all adults living with HIV/AIDS Specifically, 76% of all HIV-positive women live in this region. Adult HIV Prevalence 7

8 Morbidity U.S. Since 1981, it is estimated that 1.7 million people in the U.S. have been infected with HIV. The CDC estimates that about 1.2 million people in the United States are living with HIV. Roughly, 50,000 people in the United States every year are infected with HIV (2009). Possibly upwards of 20% of those individuals do not know they are infected (2008). Morbidity U.S. More individuals are being diagnosed with HIV earlier in the course of their infection. However, about one-third (32%) of CDC reported HIV patients were diagnosed with AIDS, within 12 months of their initial HIV diagnosis (2008). The majority of individuals diagnosed with HIV and AIDS in 2008 resided in urban areas with more than 500,000 people. Morbidity by Group African Americans represent approximately 44% of new HIV infections, but only 14% of the U.S. population (2009). African American men s rate of new HIV infections was six times that of white men, and nearly two and a half times that of Hispanic/Latino men. The estimated rate of new HIV infection for African American women was 15 times the rate for white women. 8

9 Group Breakdown (2009) Question 3 Roughly how many Americans have died of AIDS since the epidemic began in 1980? , , , ,000 Mortality - National In the United States, 619,000 people have lost their lives due to AIDS since ,000 more Americans died, just in HIV/AIDS is now the leading cause of death among African-American American women between the ages of The projected life expectancy for HIV/AIDS patients is 24.2 years for patients. 9

10 What are the other health concerns? Co-morbidities Co-Morbidities Hepatitis A, B, C, and E Autoimmune Hepatitis Human Papilloma Virus (HPV) HIV 2 Syphilis Seizure Disorders Rheumatic Disorders Precaution in using corticosteroids and immunosuppressant agents due to increased risk of stimulating viral replication. Leprosy, Malaria, Helminthes, and Chagas Disease Systemic Diseases Myocardial infarction: A two-fold increase in the relative risk has been observed in the HIV-positive population. Osteoporosis: A three-times times greater prevalence. Renal diseases: African American HIV patients are more likely to develop chronic kidney failure HIV-infected patients have a decreased GFR and increased prevalence of microalbuminuria 10

11 How does it happen? Pathophysiology Transmission Pathway The HIV virus first enters the body by binding with Macrophages and dendritic cells (DC s) on the surface of genital mucous membranes. Because HIV attaches to the macrophages, before it finds a host cell, it is essentially cloaked. It is then is shuttled the lymph nodes which are rich in CD4 T-Cell T Lymphocytes or Helper T-Cells. T Next, the HIV virus then attaches itself to the CD4+ T-Cell T Lymphocytes. The Virus 11

12 Cloaking Infected CD4 Cell CD4 Cell with HIV Enlarged View Viral Reproduction The CD4+ cells direct the immune system s response pathway and are an integral part of cell- mediated immunity. HIV is a retrovirus and utilizes the reverse transcriptase enzyme to direct host CD4 s own RNA to replicate the virus s RNA. The cell then supports and replicates the virus, releasing new virions to infect additional CD4+ cells. 12

13 Immune Response Cytotoxic lymphocyte production follows the rise of HIV in the blood. CD4+ and CD8+ cells are produced to direct the immune response the virus, with seroconversion to the HIV antibodies occurring at three to six months. The struggle then begins between increasing the HIV viral load and the CD4+ production. Left unchecked the HIV virus overwhelms the immune system s capability. CD4 vs. Viral Load Disease Phases Acute Phase or AIDS-related complex : Symptoms appear about days post infection. About 40-90% of patients experience flu-like like symptoms. Acute symptoms: : fever, inflamed lymph nodes, headache, sore throat, diarrhea, fever, and rash.* * However, in some cases there are no symptoms at all. Chronic Phase or Asymptomatic Stage AIDS Phase Opportunistic Infections Co-morbidities and Systemic Diseases 13

14 Defining AIDS The diagnostic criteria for the transition from HIV infection to AIDS is a CD4+ T-Helper T count that is below 200 cells/ml and/or the development of an AIDS-defining clinical condition or Opportunistic Infection (OI s). Opportunistic Infections Bacterial Infections: Bacterial Diarrhea Tuberculosis (TB) Syphilis & Neurosyphilis Bacterial Pneumonia Fungal Infections: Aspergilosis Candidiasis Coccidioidomycosis Histoplasmosis Protozoal Infections: Cryptosporidiosis Psoriasis Pneumocystis Pneumonia Toxoplasmosis Malignancies: Anal Dysplasia/Cancer Cervical Dysplasia Kaposi's Sarcoma (KS) Lymphomas Viral Infections: Hepatitis C Herpes Virus (Shingles) Herpes Simplex Virus Human Papiloma Virus (HPV) Neurological Conditions: AIDS Dementia Complex (ADC) Peripheral Neuropathy When to intervene? Treatment 14

15 It Depends Initially, there is no HIV specific treatment to be given in the Acute Phase supportive measures only. The initial treatment goal is to preserve patients in their drug-free period for as long as possible. Regular monitoring of CD4+ count of therapy naïve patients is therefore essential. Treatment Dilemma: Once therapy is started, the antiretroviral regimens must be continued for the remainder of their lives. Antiretroviral Therapy (ART) In 1987 the first Antiretroviral Therapy (ART) that was used against the HIV-1 1 virus was zidovudine(azt) (AZT). It was originally hoped that HIV- 1 could be eradicated from the body. Unfortunately, only virus suppression is the best that can be achieved by continuous ART. ART failure is usually due to low compliance, evolution of drug-resistant resistant HIV-1 1 variants, and/or medication side effects. HAART In 1996 treatment shifted from drug Cocktails to ART Combination therapy, then finally to Highly Active Anti-Retroviral Therapy (HAART). HAART s primary goal is to prevent emergence of drug-resistant resistant HIV-1 1 variants by suppressing the viral replication to negligible levels. By utilizing multiple medications (three or more) at one time, the HIV-1 1 virus has difficulty acquiring complex combination of mutations needed to develop multi-drug resistance. 15

16 Treatment Criteria CD4+ count: Previously,, if it dropped below 350 cells/ml the patient should was closely monitored and for possible treatment. However, once the cell count fell to below 200 cells/ml HAART treatment was started immediately. In 2009 the WHO changed its cutoff to a CD4+ count below 350 cells/ml to begin early ART. HIV- Viral load: If the HIV-1 1 plasma viral load is above 100,000 per/ml. AIDS: The patient is presenting with symptoms or has signs of an AIDS-defining clinical condition (OI s) Treatment Goals The first treatment goal of HIV therapy is to prevent the CD4+ T-cell T count from dropping to less than 200 cells/ml. The is second goal is to suppress the plasma viral loads to below the level of detection, which is 50 copies/ml ml. This does not negate the need for continued treatment of the opportunistic infections once AIDS has developed. Antiretroviral Drugs Description Mechanism of Action Medication Possible Problems Nucleoside Reverse Transcriptase Inhibitors (NRT s) Competitively Inhibits HIV reverse transcriptase & DNA chain terminator Zidovudine (AZT) Didanosine (ddi ddi) Stavudine (d4t) Abacavir Emtricitabine (FTC) Lamivudine (3tc) Possible class resistance Possible Lipodystrophy Lactic Acidosis Non-nucleoside nucleoside Reverse Transcriptase Inhibitors (NNRT s) Non-competitive inhibition of reverse transcriptase Efavirenz Nevirapine Delaviridine Drug-resistance resistance development threshold is low Nucleotide Reverse Transcriptase Inhibitors (NtRT s ( NtRT s) Competitively inhibitors of viral reverse transcriptase Tenofovir (PMPA) Severe side effects Drug-resistance resistance development threshold is low 16

17 Antiretroviral Drugs Description Mechanism of Action Medication Possible Problems Protease Inhibitors Inhibits post- translational processing of gag and pol polyproteins and enzymes Saquinavir, Ritonavir, Amprenavir, Indinavir, Nelfinavir, Lopinavir, Atazanavir, Fosamprenavir, Tipranavir, Darunavir Severe side effects Significant drug interaction with wide array of other medications Fusion inhibitors Inhibit fusion of HIV-1 1 with the CD4+ cell membrane Enfuvirtide SC injection Effective only after CD4 binding and prior to membrane fusion Integrase Inhibitors (INIs) Inhibit the HIV-1 viral integration into the host's own genome Raltegravir Used in salvage therapy Antiretroviral Drugs Description Mechanism of Action Medication Possible Problems Chemokine antagonists Blocks the chemokine receptors on the cell membrane, & prevent HIV-1 1 viral entry into the cell Maraviroc (CCR5 inhibitor) First drug that targets host's factor. Only effective against R5-tropic viruses. Good for post- exposure prophylaxis. Can cause virus to switch to R4-tropism. Maturation inhibitors Prevents the maturation of P-25 P to P-24, P and stops release of viable viral particles from the CD4+ cell Bevirimat Under investigation. Occurrence of drug-resistant resistant mutations and viral augmentation Antiretroviral Drugs Summary Eight different medication classes Utilizing eight different mechanisms of action Total of Twenty-five different medications Problem Areas Drug resistance leading to viral mutations Drug Interactions with other medications Side Effects: Diarrhea, nausea, vomiting, lactic acidosis, lipodystrophy ipodystrophy, hyperglycemia, pancreatitis, liver toxicity and failure, hematologic disorders,, hypersensitivities, & rashes. 17

18 Where do we come in? Primary Care Treatment Primary Care Prevention and Education Barriers, Barriers, Barriers!!! All genital, anal, and oral sexual contact Even between two infected partners - Mutations Be a myth buster/educator Recognizing possible new infections Know the risk factors MSM, Unprotected Sex Presentation of the AIDS-related complex: The worst flu I ve ever had - fever, inflamed lymph nodes, headache, sore throat, diarrhea, fever, and rash. Primary Care Drug Interactions with HAART medications In general caution must be reserved when using: Anticonvulsants, Antimycobacterials, Antifungals, Birth Control Pills, and Benzodiazapines Because they are metabolized via the cytochrome P450, CYP3A, and CYP3A4 enzyme systems. There is a potential for the drug levels which leads to a potential for drug toxicity. Exercise greatest caution with the following: NNRTI s, NRTI s, CCR5 s, & Protease Inhibitors. Bottom Line: : Check your references first. 18

19 Primary Care Identifying new onset of OI s and/or AIDS Opportunistic Infections: Six major categories and 22 illnesses. They are not present in healthy patients. Possibly the first interaction with a provider. AIDS: It can present early or many years later in the life of the HIV positive patient. Indentifying early, beginning HAART earlier can extend the life of the patient. Highest Prevalent OI s Opportunistic Infection Candidiasis Cytomeglavirus Chronic Herpes Simplex Mycobacterium avium Complex Pneumocystis carinii Pneumonia Toxoplasmosis Tuberculosis Effected Area Mouth, Throat, Vagina Eyes and GI Mouth and Genitals Bacterial GI Tract Infection Fungal Respiratory CNS Protozoal Infection Bacterial Resp. and CNS Treatment Clotrimazole, Nystatin, Amphotericin, and/or Fluconazole Oral - Valganciclovir I.V. - Ganciclovir or Foscarnet Zovirax Macrolides, Rifamycins, Fluoroquinolones,, & Aminoglycosides TMP/SMX, Dapsone, Pentamidine, &/or Atovaquone TMP/SMX, Pyrimethamine, Sulfadiazine, Clindamycin Ethambutol, Isoniazid, Pyrazinamide, Rifampicin Who needs special attention? Pregnancy, Pediatrics, and Providers 19

20 Pregnancy Vertical transmission of HIV-1 1 during pregnancy is now limited to less than 2% (2011). The transmission can occur at three different times: Prepartum - due to the shared fetomaternal blood across the placenta. Intrapartum - when infant's oral mucosa is exposed to infected vaginal secretions. Breast feeding NOT recommended in U.S. The goal of treatment of pregnant women is successful viral suppression (Viral ( load <50 copies/ml by the time of labor). Pregnancy To achieve that goal HAART is started after the first trimester. Vaginal deliver is allowed if the mother has an undetectable plasma HIV RNA viral load. The babies of HIV-1 1 positive mothers need AZT prophylaxis. Unfortunately, breast feeding is attributed to 30% to 50% of new infant HIV infections. The highest rate has been observed in the first 3 months. Children Signs and Symptoms: Children born with HIV usually will begin to show symptoms within two years of birth. A child with HIV may grow slowly or often become sick. ART or HAART treatment depends on age (2010): Treat all infants 12 months of age or younger regardless of clinical, immunologic, or symptoms. If the child s age is >1 and <5, then treat if CD4 is <350 and/or VL is > 100,000. If the child s age 5 years (minimal or no clinical symptoms), then treat if CD4<500 and/or VL is > 100,

21 Occupational Exposure According to the CDC, only 57 health care workers have acquired HIV due to workplace exposures. There were only a few cases in which health care workers transmitted HIV to patients. All facilities should have a Finger Stick Protocol Stat HIV test to be administered immediately to both the source patient and the health care provider. If presenting under two hours from injury, the provider can wait for the results of the source patient test. If over two hours from injury to presentation, then begin prophylactic ART treatment. What s on the horizon? Currently Focus primarily has remained in the areas of education, prevention, early detection, treatment strategies, and extending longevity. Focus has been placed on early and aggressive ART treatment in high risk areas and population groups. June 2012: : First available OTC home HIV test! July 17, 2012: : First approved medication for the prevention of HIV transmission 75% reported success. The life expectancy has risen to nearly 25 years for individuals living HIV/AIDS. 21

22 Research One of the major obstacles to curing HIV infection is the ability of the HIV virus to integrate into the host genome and remain latent for years. In 2011 NIH was granted funding to begin a comprehensive five year research study with the ultimate goal of a cure for HIV. They will be utilizing three research teams focused on developing strategies that could help to rid the body of HIV. Possible Cure? The first known case of someone being cured of HIV. Timothy Ray Brown, was co-infected with leukemia and HIV. He received a bone marrow transplant and was effectively cured of his HIV. In 2011, four years after treatment, he was confirmed as having a negative HIV status. Further research is ongoing to attempt to replicate the results seen in this case.* Who We Haven t Lost 22

23 Question 1 What geographic region has the highest rate per capital of HIV infection? 1. South America 2. South East Asia 3. Southern Russia 4. Sub-Saharan Saharan Africa Question 2 By 2015, IOM estimates that the percentage of US HIV patients over 50 will be? 1. 45% 2. 50% 3. 55% 4. 60% Thank you 23

24 References Page 1 CDC, HIV Prevalence estimates U.S., MMWR 2008; 57(39): CDC, HIV Prevention in the United States at a critical crossroad, Internet Report, August, CDC Report, HIV in the United States: An Overview, CDC Online, July 2010, Modified 3/12/12. Cichocki, Mark, Top 10 HIV and AIDS Myths, About.com Guide, June 11, Crane, Jill and Johnson, David, First Report of AIDS, CDC Morbidity & Mortality Weekly Report, 6/1/01, 50/21. DeNoon, Daniel, Ten HIV/AIDS Myths, CBS News HealthWatch, November 30, Dugdale, David, C. III, HIV infection, Healthline, Wednesday, April 4, 2012 Gazzola, Linda, et. Al., Toxicities: Choosing Alternative Antiretroviral Strategies. 11/12/10; HIV Therapy. 2010;4(5): Hall, H. Irene, et. al., Estimation of HIV Incidence in the United States, JAMA, 2008; 300(5): Hutchinson AB, et.al., The economic burden of HIV in the United States in the era of highly active antiretroviral therapy: evidence of continuing racial and ethnic differences, Journal or Acquired Immune Deficiency Syndrome Dec 1; 43(4): Kates, Jennifer & Carbaugh, Alicia, The Global HIV/AIDS Epidemic, The Henry J. Kaiser Family Foundation. 5/06 Keating, Alan, AIDS in America: A Personal Interview with the Director of Infectious Disease at the National Institutes of Health, May 15, Massachusetts Medical Society. New England Journal of Medicine 339:32. Copyright NIH Staff, NIH funds new research toward an HIV cure, NIH News, July 11, References Page 2 Mazzotta, Meredith, CDC Report, Economic models show HIV treatment scale-up is cost-effective, 1/27/12. Moyer, Christine, HIV in Primary Care: Treating an Aging Epidemic, Amednews.com, 7/4/11. Pickrell, John, Timeline: HIV & AIDS, New Scientist, September 4, Reuters News Service, New U.S. HIV cases to cost $12 billion a year, Nov. 2, Staff Author, Drug-Drug Interactions Between ARV Agents, Medications Used in Substance Use Treatment, and Recreational Drugs, HIV Clinical Resource, March Staff Author, Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, AIDS Info, 8/11/2011. Staff Author, Human Immunodeficiency Virus 1 transmission, MetaPathogen.com, 10/02/11. Staff Author, OPPORTUNISTIC INFECTIONS, AIDS.org, Staff Author, What is HIV/AIDS, Beltina.org-Encyclopedia of Health. Staff, Early ART for HIV Infection Is Cost-Effective, Medscape Medical News, 9/22/11. Staff, HIV Signs and Symptoms, UCSF Medical Center Online, April 3, Staff, The HIV/AIDS Epidemic in the United States,The Henry J. Kaiser Family Foundation,February Osmond, Dennis H., Epidemiology of HIV/AIDS in the United States, HIV In Site Knowledge Base Chapter, 3/03. USAID, HIV/AIDS: Frequently Asked Questions, Online Report, February 1, Wessner, David, The Sides Effects of HAART, The AIDS Pandemic Blog,12/13/06. 24