HIV – Part II February 19, 2013 Jeff Meier, MD Infectious Diseases [email protected] Iowa MATEC www.int-med.uiowa.edu/Education/MATEC/ Case 2 33 yo WM presents with progressive dry cough for 4 wk; exertional dyspnea & vague central chest pressure for 3 wk; and fever & sweats for 2 wk T37.4, HR110, RR28, BP NL Lungs clear Many common warts on hands O2 sat 92%; with exertion, 85% WBC 3.3, ALC 200. ABG(RA) - pO2 80 HIV Ab+ and CD4 9 (1%) Atypical pneumonia - patchy bilateral air space disease Case 2 WHICH OF THE FOLLOWING WOULD NOT BE APPROPRIATE FOR THIS PATIENT? A. B. C. D. Bronchoalveolar lavage Empiric therapy for pneumocystis Primary prophylaxis for CMV Antiretroviral treatment Late HIV Diagnosis is Too Common One-third of persons have AIDS diagnosis within year of HIV diagnosis •U.S.A., ~33%; Iowa, ~40% Late diagnosis shortens life expectancy; risks HIV transmission to others Early diagnosis ~ normal life expectancy with HIV treatment MMWR. Dec 3, 2010/59(47);1550-1555 Iowa Department of Public Health Pneumocystis Pneumonia Pneumocystis jirovecii Most common AIDS-defining illness CD4<200 Trimethoprim-sulfamethoxazole (TMPSMX) started as empiric therapy DDX: TB, fungal (histoplasmosis, cryptococcus), CMV NIH, CDC, HIVMA/IDSA GUIDELINES http://www.aidsinfo.nih.gov/ Pneumocystis Pneumonia (PCP) 4-8 d is mean time to improvement with treatment Steroid for ≥ 21 d if p02 <70 (A-a >35) Maintenance Rx (oral TMP-SMX) until CD4>200 with cART (or HIV viral load adequately suppressed*) *Recent data suggests that CD4 target of >200 is overly conservative if HIV viral load suppressed NIH, CDC, HIVMA/IDSA GUIDELINES http://www.aidsinfo.nih.gov/ Primary Prophylaxis CD4<200 AIDS *If serum Toxo IgG antibody is positive CD4<100 Pneumocystis jirovecii CD4<50 Toxoplasma* Mycobacterium avium complex NIH, CDC, HIVMA/IDSA GUIDELINES http://www.aidsinfo.nih.gov/ Opportunistic Infection Prophylaxis AIDS Primary prophylaxis (prevention) Pneumocystis (start, CD4<200; stop, CD4>200) Toxoplasma Ab (start, CD4<100; stop, CD4>100-200) MAC (start, CD4<50; stop, CD4>100) Secondary prophylaxis (maintenance) Pneumocystis (stop, CD4>200) Toxoplasma (stop, CD4>200) MAC (stop, CD4>100) CMV (stop, CD4>100-150) Cryptococcus (stop, CD4>100-200) Histoplasma (stop, CD4>150) cART = 3 Active Drugs that Potentially Target Cellular Entry Receptor or HIV Reverse Transcriptase, Integrase, Protease, or Fusion Protein Goals of Treatment Suppression of HIV Replication Immune Reconstitution Decrease Transmission Risk Fusion Inhibitor (FI) Protease Inhibitors (PI) CCR5 Inhibitors RT Inhibitors Nucleoside/tide (NRTI) Non-nucleoside (NNRTI) Integrase Inhibitors (INSTI) Lifecycle cartoon from Watkins, D. Scientific American 2008 Treatment Adherence Ideal drug: Durably effective Safe Well tolerated Convenient Real world: Single Tab QD Atripla NRTI x2 NNRTI Complera NRTI x2 NNRTI Stribild NRTI x2 INSTI Booster NRTI x2 = Emtricitabine & Tenofovir When to Start Combination Antiretroviral Treatment (cART) CD4+ Cell Count • < 350 cells/mm³ Recommendation • 350-500 cells/mm³ • START • > 500 cells/mm³ • OFFER (adolescents/adults) •START Conditions Favoring Initiation of Therapy Regardless of CD4+ Cell Count • TB or AIDS-defining illness • Pregnancy & infants • HIV nephropathy • Chronic HBV (and HCV) • Age >60 International Antiviral Society-USA Panel. JAMA, July 25, 2012—Vol 308 US Department of Health and Human Services - http://aidsinfo.nih.gov/Guidelines Treatment as Prevention Early vs Delayed cART + Condoms Counseling Discordant Heterosexual Couples HPTN052 Study NEJM 2011 Early cART - 96% decrease in HIV transmission U.S. Population Cascade of Care IOWA* 38% Gardner et al. Clinical Infectious Diseases, 2011 52(6):793-800 *IDPH HIV STD Hepatitis Bureau Immune Reconstitution Inflammatory Syndrome IRIS •Definition: “Atypical inflammatory disorders associated with immune recovery”J.G. Bartlett & J.E. Gallant HIV Drug Class Characteristics Low Mod Hi HIV Drug Classes Drug-Drug Interaction Potential Special Considerations CCR5 inhibitor FI NRTI NNRTI INSTI PI Low Coreceptor tropism test before use Low Low HLA-*B5701 test prior to abacavir use^ Mod Efavirenz is teratogenic Low Hi Decrease effectiveness of birth control pills ^Hi risk of abacavir hypersensitivity reaction with positive HLA-*B5701 status Case 3 CC: Loss of vision HIV+ man, CD4 350 (19%) Thrush 2 mo ago Rash 1 wk ago; Rx with prednisone HA for several days PE: Rash - face, limbs, torso, palms & soles Head CT normal LP: OP 16 cm; 52 L & 3 N; protein 87; glucose 48 Case 3 Serum RPR 1:256, TP-TA positive WHICH OF THE FOLLOWING STATEMENTS ABOUT SECONDARY SYPHILIS IS TRUE? A. Increasing incidence in women B. Spares the eye C. Rarely involves oral mucosa D. Occurs at any CD4 count Increase in 1o & 2o Syphilis Rates in Men http://www.cdc.gov/ Secondary Syphilis Macular-Papular Rash Palmar-Plantar Rash Infectious Diseases, UIHC Infectious Diseases, UIHC Secondary Syphilis Infectious Diseases, UIHC STD Atlas, 1997 STD Atlas, 1997 J. Engelman, San Francisco City Clinic Mucous patches Condyloma lata Case 4 42 yo HIV+ man reports bleeding from anus and enlarging anal lesion. Had anal wart fulgurated by local GI doctor last year. H/O AIDS (CD4 nadir, 55 cells/mm3). Now, receiving cART, with CD4 count of 355 (19%) and HIV viral load <50 copies/mL. Has HIV-associated lipodystrophy, type II diabetes mellitus, mixed hyperlipidemia, and hypertension. Case 4 PRIOR HISTORY OF AIDS INCREASES RISK FOR… A. B. C. D. Dyslipidemia Cardiovascular disease Squamous cell carcinoma of anus All of the above Metabolic Syndrome Central obesity Hypertension High triglycerides Low HDL Insulin resistance L4 level Lipodystrophy Fat Atrophy Fat Atrophy Visceral Fat Serious Non-AIDS Disease: Top 3 1) Malignancies 2) Cardiovascular disease 3) Liver failure (hep B & C) The lower the CD4 count nadir (lowest value ever), the greater the risk of lifethreatening non-AIDS-defining illnesses HPV-Related Anal Cancer Earlier Age HIV+ Diagnosed among US Veterans (N=1112), 19982004 HIV- Chiao EL, et al. J Clin Oncol. 2008. 26:474-9 May arise from or mimic wart Need not have analreceptive intercourse HPV4 Vaccine Gardasil protects against anal disease (AIN) in young MSM (ages, 16-24); 51-78% effective FDA-Approved Product Insert CONCLUSION The epidemic continues cART is a life-saver and prevents spread Now a manageable chronic disease Have low threshold to test Hotlines: Warmline 1-800-933-3413 PEPline 1-888-HIV-4911 Perinatal Hotline 1-888-448-8765 NIH, CDC, HIVMA/IDSA Guidelines: http://www.aidsinfo.nih.gov/ •Antiretroviral therapy •Prevention & Rx for opportunistic infections •Pregnancy •Children/adolescences