HIV Part II. February 19, Jeff Meier, MD Infectious Diseases Iowa MATEC.

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1 HIV Part II February 19, 2013 Jeff Meier, MD Infectious Diseases Iowa MATEC

2 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%)

3 Atypical pneumonia - patchy bilateral air space disease

4 Case 2 WHICH OF THE FOLLOWING WOULD NOT BE APPROPRIATE FOR THIS PATIENT? A. Bronchoalveolar lavage B. Empiric therapy for pneumocystis C. Primary prophylaxis for CMV D. Antiretroviral treatment

5 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); Iowa Department of Public Health

6 Pneumocystis Pneumonia Pneumocystis jirovecii Most common AIDS-defining illness CD4<200 Trimethoprim-sulfamethoxazole (TMP- SMX) started as empiric therapy DDX: TB, fungal (histoplasmosis, cryptococcus), CMV NIH, CDC, HIVMA/IDSA GUIDELINES

7 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

8 Primary Prophylaxis AIDS CD4<200 Pneumocystis jirovecii CD4<50 *If serum Toxo IgG antibody is positive CD4<100 Toxoplasma* Mycobacterium avium complex NIH, CDC, HIVMA/IDSA GUIDELINES

9 Opportunistic Infection Prophylaxis AIDS Primary prophylaxis (prevention) Pneumocystis (start, CD4<200; stop, CD4>200) Toxoplasma Ab (start, CD4<100; stop, CD4> ) 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> ) Cryptococcus (stop, CD4> ) Histoplasma (stop, CD4>150)

10 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

11 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

12 Treatment Adherence Ideal drug: Durably effective Safe Well tolerated Convenient Real world: Atripla Complera Stribild Single Tab QD NRTI x2 NNRTI NRTI x2 NNRTI NRTI x2 INSTI Booster NRTI x2 = Emtricitabine & Tenofovir

13 When to Start Combination Antiretroviral Treatment (cart) CD4+ Cell Count < 350 cells/mm³ cells/mm³ Recommendation START START > 500 cells/mm³ OFFER (adolescents/adults) 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 -

14 Treatment as Prevention Early vs Delayed cart + Condoms Counseling Discordant Heterosexual Couples HPTN052 Study NEJM 2011 Early cart - 96% decrease in HIV transmission

15 Cascade of Care U.S. Population IOWA* 38% Gardner et al. Clinical Infectious Diseases, (6): *IDPH HIV STD Hepatitis Bureau

16 Immune Reconstitution Inflammatory Syndrome IRIS Definition: Atypical inflammatory disorders associated with immune recovery J.G. Bartlett & J.E. Gallant

17 HIV Drug Class Characteristics HIV Drug Classes CCR5 inhibitor FI NRTI NNRTI INSTI PI Low Mod Hi Drug-Drug Interaction Potential Low Low Low Mod Low Hi Special Considerations Coreceptor tropism test before use HLA-*B5701 test prior to abacavir use^ Efavirenz is teratogenic Decrease effectiveness of birth control pills ^Hi risk of abacavir hypersensitivity reaction with positive HLA-*B5701 status

18 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 Case 3 LP: OP 16 cm; 52 L & 3 N; protein 87; glucose 48

19 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

20 Increase in 1 o & 2 o Syphilis Rates in Men

21 Secondary Syphilis Macular-Papular Rash Palmar-Plantar Rash Infectious Diseases, UIHC Infectious Diseases, UIHC

22 Secondary Syphilis Infectious Diseases, UIHC STD Atlas, 1997 STD Atlas, 1997 Mucous patches J. Engelman, San Francisco City Clinic Condyloma lata

23 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.

24 Case 4 PRIOR HISTORY OF AIDS INCREASES RISK FOR A. Dyslipidemia B. Cardiovascular disease C. Squamous cell carcinoma of anus D. All of the above

25 Metabolic Syndrome Central obesity Hypertension High triglycerides Low HDL Insulin resistance L4 level Fat Atrophy Fat Atrophy Lipodystrophy Visceral Fat

26 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

27 HPV-Related Anal Cancer Earlier Age HIV + HIV - Diagnosed among US Veterans (N=1112), Chiao EL, et al. J Clin Oncol :474-9 May arise from or mimic wart Need not have analreceptive intercourse

28 HPV4 Vaccine Gardasil protects against anal disease (AIN) in young MSM (ages, 16-24); 51-78% effective FDA-Approved Product Insert

29 CONCLUSION The epidemic continues cart is a life-saver and prevents spread Now a manageable chronic disease Have low threshold to test Hotlines: Warmline PEPline HIV-4911 Perinatal Hotline NIH, CDC, HIVMA/IDSA Guidelines: Antiretroviral therapy Prevention & Rx for opportunistic infections Pregnancy Children/adolescences

Combination Anti-Retroviral Therapy (CART) - Rationale and Recommendation. M Dinaker. Fig.1: Effect of CART on CD4 and viral load

Combination Anti-Retroviral Therapy (CART) - Rationale and Recommendation M Dinaker INTRODUCTION The wide availability of effective, safe and mostly well tolerated combined anti-retroviral therapy (CART)