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Antiretrovirals for HIV Prevention: Progress and Challenges

Antiretrovirals for HIV Prevention: Progress and Challenges. Kenneth H. Mayer, M.D. Brown/Miriam/Fenway. HIV PREVENTION 2010. DECREASE SOURCE OF INFECTION Barrier protection Blood screening IDU harm reduction STI Treatment? Antiretroviral Therapy PMTCT

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Antiretrovirals for HIV Prevention: Progress and Challenges

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  1. Antiretrovirals for HIV Prevention: Progress and Challenges Kenneth H. Mayer, M.D. Brown/Miriam/Fenway

  2. HIV PREVENTION 2010 • DECREASE SOURCE OF INFECTION • Barrier protection • Blood screening • IDU harm reduction • STI Treatment? • Antiretroviral Therapy • PMTCT • Rx infected partners • DECREASE HOST SUSCEPTIBILITY • Barrier protection • Infection Control • Circumcision • Vaccines? • STI Treatment? • PEP • Oral PREP • Topical Microbicides • ALTER BEHAVIOR • Condom and HIV testing promotion • Individual interventions • Couples interventions • Community-based interventions • Structural interventions (e.g., economic)

  3. HOW ANTIRETROVIRALS CAN AFFECT HIV TRANSMISSION PLASMA   SURVIVAL HIV  PLHIV   GENITAL TRACT DURATION OF HIV INFECTIOUSNESS   TRANSMISSIONTRANSMISSION • RELEVANT ISSUES: ACCESS, ADHERENCE, PREVENTION, STI RX.

  4. On ARV Off ARV Treatment as Prevention: Discordant Couples HIV-free Survival of HIV- partners,by ARV status of HIV+ Partner 2,993 couples were followed for a median of 512 days Sexual risk behaviors lower in those on ART (19% vs 25%, P<0.05) Both ART and change in behavior independently reduced HIV transmission Sullivan P. CROI 2009 1.0 0.8 CensoredLogrank P<.0001 0.6 Survival Probability 0.4 0.2 0.0 2073920 1035475 598256 25269 806 00 0 500 1000 1500 2000 2500 Days Donnell, D. CROI, 2010: 1 linked transmission in Partners study from one person who had been on HAART for 18 days in a sample with 236 py f/u, compared to 2.23% incidence in untreated couples Over 90% decrease in HIV transmission with HAART

  5. Can Antiretrorivals ↓ HIV Transmission? • HIV in several countries where treatment and prevention have been integrated, e.g. Brazil and Taiwan (Porco, AIDS, 2004; Fang, JID, 2004) Counter: Resistant HIV transmission (Imrie, JID, 1997;Little, NEJM, 2002;Angarano, AIDS, 2004) but prevalence may be decreasing because of HAART efficacy(Routy, AIDS, 2004) • MSM: ↓ Community Viral Load, ↓ HIV incidence in SF (Das-Douglas, CROI, 2010, Session 10, 2/17) • Counter: ↑ HIV incidence in Amsterdam MSM • (Jansen, CROI 2010, Session 10, 2/17) • HPTN 052 will answer whether starting earlier treatment can decrease HIV incidence • But, Cell-Associated HIV is a major source of infectious virus (Anderson et al, AIDS, 2010)

  6. HPTN 065 (TLC Plus) Testing, Linkage to Care, Treatment, Plus Lots More…. Initiation of ART Testing Adherence to ART Linkage to care Positive Prevention Decrease in HIV Transmission Test HIV Positive Adopt safer behaviors Enroll in Care Treat Maintain viral suppression

  7. Why Antiretrovirals for 1° Prevention? • Non-human primates • Multiple drugs have been shown to decrease HIV transmission pre or post exposure • PMTCT, even single dose NVP to Mother/Infant was protective • ? Enough time to lower VL in mother • ? Direct infant benefit from antiretrovirals • Occupational Post Exposure Prophylaxis (PEP) after percutaneous exposures • Associated with lower risk in HCW • AZT alone associated with 80% decrease • Not RCT, retrospective case-control MMWR 2005

  8. Non-Occupational PEPSchechter et al, JAIDS, 2004 • N=200 high risk Brazilian MSM • Followed over 24.2 months • PEP (AZT/3TC) 4 day starter pack • 28 day course • 68 used PEP 109 times • HIV incidence 2.9/100py • 10 infected who did not use PEP (N=132) • Assumed partner was HIV-Uninfected • 1 infection in a PEP user (N=68) • Risk Behavior Decreased Similar to SF experience (Martin et al, AIDS, 2004)

  9. Study to assess most effective modality for topical ARV gels 1% TDF or 1% TDF/5% FTC gels in 23 macaques Gel (matrix + preservatives) clear, viscous, odorless, stable at 37° x 6 months 3 ml gel applied 30 mins before vaginal challenge with R5 virus inoculum (10 TCID50) Challenges 2x/week for total 20 challenges Topical PrEP in Macaques with TDF or TDF/FTC no gel (n=2) placebo gel (n=9) FTC/TDF gel (n=6) TDF gel (n=6) 100 75 50 % Protected 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Challenges Dobard C, et al, CROI, 2009; Dobard et al, CROI, 2010, poster 949

  10. What if PrEP “Works”? • Block other steps in HIV life cycle, e.g. binding and integration? Develop drugs just for prevention? • New Co-formulations: Generic PrEP? • Topical vs. Oral: VOICE and beyond • What is the optimal drug delivery system: gel, ring, suppository, diaphragm, injection, or pill? • How to best dose: Fixed intervals vs. pre/post coital? • PrEP and the immune system: adjuvant for vaccines? • Special populations: youth, pregnant women

  11. What if PrEP “Works”? • Who should prescribe: How best to train providers? • How will access be ensured in resource-limited settings? • Prevention package: What is optimal counseling? • How to often to monitor: safety labs, and test for new HIV infection/resistance? Home testing? • How to facilitate best practices? New roles for ASO’s; use of new media to educate • Will need enhanced surveillancefor intended (decreased HIV incidence) and unintended (risk compensation, resistance) consequences

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