Core Curriculum Review: HIV

1. Core Curriculum Review:HIV Jason M . Leider, M.D., Ph.D. NBHN Associate Medical Director of HIV Services Associate Professor of Internal Medicine, AECOM

2. Occupational Bloodborne Exposuresfocus on HIV • HIV, HBV, HCV are the primary agents • Risk of infection: • HBV = 27-47% • HCV = 1.9% (range 0%-22%) • HIV = 0.32% • HIV PEP: based on in vitro evidence, maternal-fetal transmission studies, retrospective case-control studies of occup HIV infxn & recent clinical experience • PEP is based on type of exposure (hollow-bore needles), depth of penetration, type of host

3. HIV pathogenesis • High replication rate (even during asymptomatic early phase) • High mutation rate: abilty to generate mutiple quasi-species

4. Natural history of HIV-1 infection over time Clinical Latency Pre-AIDS conditions Asymptomatic Persistent Generalized LNopathy Acute Retroviral Syndrome Fever PM sweats Diarrhea Wt loss CD4 = 200 7-10 yrs

5. A global view of HIV infection 33 million people [30–36 million] living with HIV, 2007 2.2

6. USA HIV facts • PLWHA = 1.1 million • 25% PLWHA are unaware of their HIV dx • AIDS (but not HIV infxn) is reportable in all 50 states • 2004: 73% new cases in M (globally, M=F) • 56,300 new HIV infxns occurred in 2006 • AA & Hisp = 70% new cases

17. Sequence of reactivity of diagnostic tests for HIV in early infection

18. Rapid HIV tests • Results in < 20 min • Oral or blood tests • Sensitivity & specificity > 99% (similar to conventional HIV enzyme immunosorbent tests

19. Four FDA-approved Rapid HIV Tests

20. US Public Health Service algorithm for serologic diagnosis of HIV-1/HIV-2 infection. 

21. Risk Assessment Guidelines for HIV+ Patients • Screen for risk behaviors: IDU, anal intercourse • Establish past/present h/o psychiatric dz, substance abuse • Open-ended questions for sx’s of STDs • Sx’s prompt STD testing

24. INITIAL F: screen for syphilis, trichomonas, GC, chlamydia M: screen for syphilis, consider sceening for GC, chlamydia (depending on local STD prevalence) SUBSEQUENT Repeat screening at least annually (or as often as 3-6 months) F of childbearing potential: routinely test for pregnancy if indicated, counsel on contraception, family planning Initial, subsequent Visits for STDs in HIV+ Patients

26. According to the US CDC definition, you have AIDSif you are infected with HIV and present with one of the following: • A CD4+ < 200 cells/µl or CD4+% < 14% • Or one of the following defining illnesses: • Candidiasis of bronchi, trachea, or lungs • Candidiasis esophageal • Cervical cancer (invasive) • Coccidioidomycosis, disseminated or extrapulmonary • Cryptococcosis, extrapulmonary • Cryptosporidiosis, chronic intestinal for longer than 1 month • Cytomegalovirusdisease (other than liver, spleen or lymph nodes • Encephalopathy (HIV-related) • Herpes simplex: chronic ulcer(s) (for more than 1 month); or bronchitis, pneumonitis, or esophagitis • Histoplasmosis, disseminated or extrapulmonary • Isosporiasis, chronic intestinal (for more than 1 month) • Kaposi's sarcoma • LymphomaBurkitt's, immunoblastic or primary brain • Mycobacterium avium complex • Mycobacterium, other species, disseminated or extrapulmonary • Pneumocystis jiroveci pneumonia (formerly Pneumocystis carinii) • Pneumonia (recurrent) • Progressive multifocal leukoencephalopathy • Salmonella septicemia (recurrent) • Toxoplasmosisof the brain • Tuberculosis • Wasting syndrome due to HIV

27. Typical relation of clinical manifestations to the CD4+ T-lymphocyte count in HIV-infected patients

28. Complications in HAART Era Squamous cell cancer of cervix due to HPV Chronic HBV Chronic HCV Squamous cell cancer of anus due to HPV (high grade abnlties need f/u w/ hi resolution anoscopy, bx)-> tx is topical imiquimod, podophylotoxin; laser, surgical cold scalpel excision

29. Follow-up Recommendations for Abnormal Cervical Cytology From Kaplan JE, Masur H, Holmes KK; USPHS; Infectious Disease Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons – 2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 51 (RR-8):1–52, 2002.

30. HIV+/HBV+ Co-infected Patients • 10% of HIV+ pts also have HBV • HIV/HBV pts have incr’d ESLD & death due to HBV than HBV only pts • HBSAg+ pts: check HBeAg, HBeAb • Check ast, alt, bili, alb, PT, HBV DNA • HBV DNA helps monitor response to tx, not prognosis • Liver bx is best to determine prognosis

31. Tx of HIV+/HBV+ Patients • Candidates: active liver inflamm, incr’d alt/ast, HBeAg+, HBV DNA > 105 c/mL • PEG IFN • Lamivudine (3TC) leads to HBeAg seroconv in 22% of tx’d pts, but easy to develop resistance • Tenofovir + 3TC or Adefovir + 3TC are better than 3TC monotx • Baraclude (Entecavir) Not Recommended for HIV/HBV Co-Infected Patients Who Are Not Also Receiving HAART Due to Potential for Development of HIV Resistance

32. HIV+/HCV+ Co-infected Patients • 30-40% of HIV+ pts also have HCV • HIV/HBV pts have incr’d ESLD & death due to HCV than HCV only pts • 70% HCV+ pts are geno 1 • Response rate to tx best for geno 2,3; worse for geno 1, 4 • HCV RNA helps for response to tx, not prognosis • Liver bx is best to determine prognosis

33. Tx of HIV+/HCV+ Patients • PEG IFN/RBV • HCV only, geno 1: Cure rates = 30-40% • HCV only, geno 2,3: Cure rates = 70-80% • APRICOT study: SVR = 40% (62% for geno 2,3; 29% geno 1) • For geno 1, HCV VL > 800,000 c/mL: SVR = 19%

35. Progression of HIV disease to AIDS or death by initial CD4 count 

36. HAART strategy in 1996 • Hit early, hit hard: CD4<500, VL > 10,000 c/mL • Changed due to: • toxicities assoc w/ HAART, • failure to demonstrate clinical benefit, • concerns about resistance • Cost of HAART = $10k to $15k/yr in USA

37. Likelihood of progression to AIDS or death in the pretreatment (A) and treatment (B) era. 

38. Indications for Initiation of Therapy: Chronic Infection

39. Indications for Initiation of Therapy: Chronic Infection

40. NRTI Abacavir ABC Didanosine DDI Emtricitabine FTC Lamivudine 3TC Stavudine D4T Zidovudine ZDV Tenofovir TDF NNRTI Delavirdine DLV Efavirenz EFV Nevirapine NVP Etravirine ETV Integrase Inhibitor Raltegravir RAL PI Amprenavir APV Atazanavir ATV Darunavir DRV Fosamprenavir FPV Indinavir IDV Lopinavir LPV Nelfinavir NFV Ritonavir RTV Saquinavir SQV hard gel HGC tablet INV Tipranavir TPV Fusion Inhibitor/Entry Inhibitor Enfuvirtide T-20 Maraviroc MVC Current Antiretroviral Medications

41. Initial Treatment: Preferred Components *Avoid in pregnant women and women with significant pregnancy potential. **Emtricitabine can be used in place of lamivudine and vice versa. NNRTI Option NRTI Options • Tenofovir + emtricitabine** • Zidovudine + lamivudine** OR + PI Options

42. Use of HIV RNA & CD4+ T Cell Levels to Guide Therapy Decisions • Syndrome consistent with acute HIV infection • Initial evaluation of new HIV diagnosis • Every 3-4 months in the untreated patient • Immediately prior to initiating therapy • 2-8 weeks after initiating therapy • Every 3-4 months in patients on therapy • As clinically indicated

43. Testing for Drug Resistance • Adjunct to guide antiretroviral therapy • Combine with obtaining a drug history and maximizing drug adherence • Research supports use in certain settings • Genotyping vs. phenotyping • Limitations of resistance testing and specific indications

44. The Use of Drug Resistance Testing

45. The Use of Drug Resistance Testing

46. Complications of HAART • Metabolic • Insulin resistance • Protease inhibitors • Hyperlipidemia (high chol/LDL/trig) • Assoc w/ most PI’s except unboosted ATV • Body fat redistribution (lipodystrophy) • Lipoatrophy: loss of facial fat/limbs • Esp assoc with stavudine • Low long-term risk for CV dz?

47. Prognosis with HAART tx • HAART can: • Suppress viral replication • Permit adquate immune system recovery • Lasting concerns: • long-term adherence • SE mgmt (esp CV events) • HAART is not a cure (cannot eliminate long-lived T-cell population)