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| Paper #26LB Pre-exposure Prophylaxis for HIV in Women: Daily Oral Tenofovir, Oral Tenofovir/Emtricitabine, or Vaginal Tenofovir Gel in the VOICE Study (MTN 003) Jeanne Marrazzo*1, G Ramjee2, G Nair3, T Palanee4, B Mkhize5, C Nakabiito6, M Taljaard7, J Piper8, K Gomez Feliciano9, M Chirenje10, and VOICE Study Team 1Univ of Washington, Seattle, US; 2HIV Prevention Res Unit, Durban, South Africa; 3CAPRISA-eThekwini CRS, Duban, South Africa; 4Witwatersrand Reproductive Hlth & HIV Inst; 5Perinatal HIV Res Unit, Johannesburg, South Africa; 6Makerere-Johns Hopkins Univ Res Collaboration, Kampala, Uganda; 7Aurum Inst, Klerksdorp, South Africa; 8Division of AIDS, NIH, Bethesda, MD, US; 9FHI360, Research Triangle Park, NC, US; and 10Univ of Zimbabwe-UCSF CTU, Harare Background: Data on the efficacy of tenofovir-based pre-exposure prophylaxis (PrEP) in women used as a daily oral pill or as vaginal gel has been mixed, and directly associated with adherence. We enrolled women in a 5-arm, randomized, double-blind, placebo-controlled trial assessing safety and efficacy of daily use of oral tenofovir (TDF), oral tenofovir/emtricitabine (TDF/FTC), and 1% vaginal tenofovir gel (TFV). Methods: From September 2009-June 2011, 12,379 women were screened at 15 sites in South Africa (Durban, Johannesburg, Klerksdorp), Uganda (Kampala), and Zimbabwe (Harare, Chitungwiza). Eligibility criteria included normal renal, hematologic and hepatic function, report of vaginal intercourse in prior 3 months, negative pregnancy test, and willingness to use effective contraception throughout study. HIV testing was done monthly, and plasma TDF levels measured quarterly. Results: Of 5029 participants, most were from Durban (3110 (61.8%)), followed by Johannesburg (704 [14.0%]), Zimbabwe (630 [12.5%]), Uganda (322 [6.4%]), and Klerksdorp (263 [5.2%]). Mean age was 25.3 years; 79% were unmarried. Over follow-up of 5511 person-years, end-of-study retention was 91%. 334 seroconversion events occurred, including 22 infections defined as acute HIV with RNA present at enrollment. Excluding these 22 participants, HIV incidence was 5.7 per 100 person-years, and ranged from 0.8 to 9.9 per 100 person-years by site. Effectiveness was –48.8% for TDF (hazard ratio [HR] 1.49; 95% confidence interval [CI] 0.97, 2.29), –4.2% for TDF/FTC (hazard ratio [HR] 1.04; 95%CI 0.73, 1.49), and 14.7% for TFV gel (HR 0.85; 95%CI 0.6, 1.2). In a case-cohort subset, TFV was detected on average in 28% of available quarterly plasma samples among participants randomized to TDF, 29% to TDF/FTC, and 22% to TFV gel. Predictors of plasma TFV detection in the case cohort group were being married, age >25 years, and reporting a primary male partner >28 years. No safety concerns were identified. Conclusions: In this population of predominately young unmarried women with high HIV incidence, adherence to study drugs was low, and no study drug significantly reduced risk of HIV acquisition. The VOICE results are consistent with FemPrEP and suggest that products that are long acting and require minimal daily adherence may be more suitable for this population. Understanding of HIV risk perception and biomedical, social and cultural determinants of adherence in this high-risk population is urgently needed.
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