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A Shot in the Arm for HIV Prevention? Opportunities and Challenges in 2016

A Shot in the Arm for HIV Prevention? Opportunities and Challenges in 2016. Jeanne M. Marrazzo , MD, MPH Professor of Medicine University of Washington Seattle, Washington. FORMATTED: 11/17/15. New Orleans, Louisiana: December 15-17, 2015. Learning Objectives.

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A Shot in the Arm for HIV Prevention? Opportunities and Challenges in 2016

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  1. A Shot in the Arm for HIV Prevention? Opportunities and Challenges in 2016 Jeanne M. Marrazzo, MD, MPH Professor of Medicine University of Washington Seattle, Washington FORMATTED: 11/17/15 New Orleans, Louisiana: December 15-17, 2015

  2. Learning Objectives • Discuss the approach to transitioning from PrEP to PEP • Define contraindications to initiating antiretroviral PrEP • Discuss accurate counseling messages for men who elect to use TDF-FTC as PrEP After attending this presentation, participants will be able to:

  3. Slide 4 of 34 Discussion • HIV incidence: two snapshots & a case • MSM in U.S. • Young women in sub-Saharan Africa • Understanding the evidence for new prevention options & implementation • Pre-exposure prophylaxis with antiretrovirals (PrEP) • Multipurpose prevention • Unintended consequences?

  4. Slide 5 of 34 One third of new HIV infections globally occur in young African women • In context of ART scale up with 40% of HIV+ persons on ART & 6 million medical male circumcisions performed by end of 2013 • Need to implement effective primary prevention strategies

  5. Slide 6 of 34 Diagnoses of HIV Infection among Adults and Adolescents, by Transmission Category, 2009–2013 — United States and 6 Dependent Areas Accounts for 81% of transmissions among men; increase highest in 25-34 y.o. Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.

  6. Slide 7 of 34 Rene P, 20 yo man, referred by partner “who had syphilis” • Considers himself healthy, no symptoms • HIV Ag-Ab test negative last week • Last syphilis serology negative 3 months ago • Two episodes of rectal gonorrhea last year • Moved to U.S. from Mexico last year • Sometimes uses meth on weekends • 6 partners in last 3 months, some anonymous. Last unprotected sex 12 h ago

  7. Slide 9 of 34 Rene P, 21 yo man, referred by a partner “who had syphilis” • What do you do?

  8. Slide 10 of 34 Rene P, 21 yo man, referred by partner “who had syphilis” • Send confirmatory syphilis test (EIA, TPPA) before treating for syphilis • Treat him with BZN PCN 2.4 x 10-6 mu IM weekly for three weeks • Check plasma HIV viral load • Offer him TDF-FTC as PrEP and see him in 3 months • Treat now for sexual PEP (TDF/FTC/raltegravir)

  9. Slide 11 of 34 HIV Prevention in Clinical Care Settings: 2014 Recommendations of the International Antiviral Society-USA Panel: Emphasized biobehavioralnature of the interventions needed Marrazzo JM, Holtgrave DR, del Rio C et al, JAMA 2014 Free web access to the paper at jama.com

  10. Antiretroviral Prevention: A Timeline Slide 12 of 34 1995 PMPA effective in macaque 2010 CAPRISA 004 Phase 2B 2006 HPTN-059 Phase 2 2015 FACTS 001 2013 MTN-003 VOICE 2011 Partners PrEP 2015 iPerGay 2010 iPrEX 2007 TDF PrEP Study 2011 HPTN-052 2005 HPTN-050 Phase 1 2015 PROUD 2011 FEM-PrEP 2011 TDF2

  11. Efficacy of Biomedical Interventions to Prevent HIV Acquisition: Evidence from Selected Randomized Clinical Trials Modified from Ambitious Treatment Targets: Writing the Final Chapterof the AIDS Epidemic, UNAIDS, 2014

  12. Key Components of These Trials Slide 16 of 34 * Condoms, counseling, STI management

  13. Key Components of These Trials Slide 17 of 34 * Condoms, counseling, STI management

  14. Slide 18 of 34 Adherence & PrEP Efficacy Clear dose-response relationship between evidence of PrEP use & efficacy Baeten et al N Engl J Med 2012 Grant et al N Engl J Med 2010 Van Damme et al N Engl J Med 2012 Thigpen et al N Engl J Med 2012 Slide modified from J. Baeten

  15. Slide 19 of 34 Oral PrEP + ART as Prevention in High-Risk Serodiscordant Couples • Partners Demonstration Project in Africa • Oral daily TDF/FTC PrEP for HIV-uninfected partner in serodiscordant couple continued 6 mos beyond initiation of ART for infected partner • High-risk couples defined as younger age, fewer children, uncircumcised HIV-negative male, cohabitating, unprotected sex in past mo, high HIV-1 RNA in HIV-positive partner • Interim analysis • > 95% of HIV-negative partners using PrEP • 80% of HIV-positive partners have initiated ART; of these, > 90% with suppression • 96% reduction in expected infections • IRR, expected vs observed: 0.04 (95% CI: 0.01-0.19; P < .0001) • In pts with seroconversion, no TFV detectable in plasma at time of seroconversion • HIV-positive partner in 1 couple not on ART (high CD4+ count) • Other couple dissolved and HIV-negative partner in new relationship Baeten J, et al. CROI 2015. Abstract 24. Reproduced with permission.

  16. Slide 20 of 34 PrEP Safety • Rates of death, serious adverse events, and laboratory abnormalities (including renal dysfunction) very low • Not significantly different between those on PrEP and placebo • PrEP well tolerated • Adverse effects occurred in minority of subjects • GI adverse effects (e.g., nausea) more common in those receiving PrEP than placebo (< 10%, primarily during the first month only) • PrEP safe during pregnancy (Mugo JAMA 2014) • No reduction in contraceptive efficacy (Murnane AIDS 2014) • Rare acquired resistance (about 3%); 12 infections averted for each case of resistance

  17. Slide 22 of 34 Randomized, open-label trial of daily oral TDF/FTC PrEP in HIV- MSM in 13 clinics in London • Immediate (n = 267) vs • Deferred for 12 mos (n = 256) Primary endpoint: HIV infection in 12 mos • 86% reduction in risk seen over 60 wks with immediate PrEP (90% CI: 58% to 96%, P = .0002) • Number needed to treat to prevent 1 infection: 13 (90% CI: 9-25) • DMSB interrupted trial; recommended that all participants be offered PrEP Lancet 2015

  18. NEJM 14 Dec 2015 • Randomized double-blind trial of event-driven oral TDF/FTC* (n = 199) vs placebo (n = 201) (both with prevention services) in France • 2 tablets taken 2-24 hrs before sex • 1 tablet 24 hrs after sex • 1 tablet 48 hrs after first event-driven dose • Primary endpoint: HIV seroconversion

  19. Patterns of Pill Use on the Basis of Clinic Visits Molina J-M et al. N Engl J Med 2015;373:2237-2246

  20. Probability of HIV-1 Infection • 86% reduction in risk in PrEP arm (95% CI: 40% to 99%, P = .002) • Number needed to treat for 1 yr to prevent 1 infection: 18 • Median of 16 pills taken per mo in each arm Molina J-M et al. N Engl J Med 2015;373:2237-2246

  21. Slide 24 of 34 Clinical Infect Dis, Sept 2015

  22. Slide 25 of 34 PrEP in the “Real” World The Good News: • No new HIV infections in over 600 PrEP initiators at Kaiser Permanente San Francisco Volk et al. CID 2015; Image courtesy J Volk

  23. Slide 26 of 34 PrEP and STIs in >600 MSMKaiser Permanente San Francisco Expected HIV incidence with this STI incidence: 8.9% Volk et al. CID 2015 Slide courtesy J. Volk

  24. Slide 27 of 34 PrEP Demo Project (NIAID), n=557 Cohen 2015, ISSTDR HIV incidence = 0.43 cases / 100 py (95% CI 0.05-1.54) STI incidence (90 cases/100 py) stable across quarterly intervals (P> 0.1) 50.9% of participants had at least one STI during follow-up As expected, >75% of GC and >85% of CT infections were asymptomatic

  25. Slide 28 of 34 Syphilis rates among MSM: timeline Syphilis rates among MSM will soon be similar to those in the early 1980s Peterman, 2015, Expert Rev Anti Infect Ther

  26. Slide 29 of 34 A Vicious Cycle: STDs predict future HIV Risk Rectal GC or CT 1 in 15 MSM were diagnosed with HIV within 1 year.* Primary or Secondary Syphilis 1 in 18 MSM were diagnosed with HIV within 1 year.** No rectal STD or syphilis infection 1 in 53 MSM were diagnosed with HIV within 1 year.* *STD Clinic Patients, New York City. Pathela, CID 2013:57; **Matched STD/HIV Surveillance Data, New York City. Pathela, CID 2015:61

  27. Slide 30 of 34 Vaginal Rings for HIV Prevention • Goal: reliable, long-lasting, woman-initiated method to protect against HIV acquisition • ASPIRE (MTN-020) studied dapivirine, with complementary studies: • IPM 027 (efficacy & safety) • >25 completed phase I/II studies • Results anticipated early 2016

  28. Slide 31 of 34 Thoughts & Next Steps • PrEP works, when taken consistently, and is the most effective tool for preventing sexual HIV transmission we have so far • Only one ARV (TFV) available; data for women still limited • Critically dependent results coming up: • Intravaginal dapivirine ring • HPTN studies of long-acting ARV (cabotegravir, rilpivirine) • Rectal microbicide development • Combination product development • Antiretroviral + hormonal contraceptive

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