CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

14 pills/month (IQR: 8-20). Overall, 34% of pts acquired a new STIs. Safety was good with only one pt discontinuing TDF-FTC because of suspected drug-drug interaction. The rate of serious adverse events was low (9%) and similar across the study arms. Drug-related gastrointestinal adverse events (nausea, diarrhea, abdominal pain) were reported more frequently with TDF-FTC than with placebo (13% vs 6%, p=0.02). Only 2 pts (1%) in the TDF-FTC arm had transient decreases in creatinine clearance < 60 mL/mn. Conclusions: On demand PrEP with oral TDF-FTC is highly effective to reduce the incidence of HIV-infection in high risk MSM and has a good safety profile. 24 Near Elimination of HIV Transmission in a Demonstration Project of PrEP and ART Jared Baeten 1 ; Renee Heffron 1 ; Lara Kidoguchi 1 ; Nelly Mugo 2 ; Elly Katabira 3 ; Elizabeth Bukusi 2 ; Stephen Asiimwe 4 ; Jessica Haberer 5 ; Deborah Donnell 6 ; Connie Celum 1 1 University of Washington, Seattle, WA, US; 2 Kenya Medical Research Institute, Nairobi, Kenya; 3 Makerere University College of Health Sciences, Kampala, Uganda; 4 Kabwohe Clinical Research Centre, Kabwohe, Uganda; 5 Massachusetts General Hospital, Harvard Medical School, Boston, MA, US; 6 Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US Background: Antiretroviral-based HIV prevention interventions, including pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), showed high efficacy for HIV protection in clinical trials among African HIV serodiscordant couples. Assessing the effectiveness of these interventions, and their ability to complement one another, in implementation settings is a priority. Methods: We are conducting the Partners Demonstration Project, an open-label, prospective study of PrEP and ART delivery among antiretroviral-naïve high-risk heterosexual HIV serodiscordant couples in Kenya and Uganda. High-risk couples are defined by a validated risk scoring tool (Kahle et al., JAIDS 2013). PrEP is offered as a ‘bridge’ to ART in the partnership – i.e., until ART initiation by the HIV-infected partner and for the first 6 months after ART is started; ART is recommended following national ART guidelines – initially CD4 <350 cells/ m L but more recently all HIV serodiscordant couples regardless of CD4 count. To assess the impact of the PrEP as a bridge to ART strategy on HIV transmission, we compared observed HIV incidence to a counterfactual simulation model, using bootstrapping methods and constructed with data from a prior prospective study of HIV serodiscordant couples (the Partners PrEP Study, placebo arm), sampled selecting for a subset with an identical distribution of risk scores and duration of follow-up. Results: Enrollment in the Partners Demonstration Project began in November 2012 and completed in August 2014, with a final sample size of 1013 couples. Given the risk score distribution of the study population, the counterfactual simulations predicted 21.7 HIV infections would be expected to date in this population (incidence 5.3 per 100 person-years, 95% CI 3.2-7.6). However, through July 2014, only one incident HIV infection has been observed during 440 person-years of follow-up, for an observed HIV incidence of 0.2 per 100 person-years (95% CI 0.0-1.3, p<0.0001 versus predicted) (Figure). PrEP was used during 47% of the 440 person-years of follow-up, ART 17%, both 25%, and neither 11%.The one transmission occurred in the absence of ART and with evidence of low PrEP adherence. Conclusions: Early results from this demonstration project integrating time-limited PrEP and ART for HIV prevention in African couples show near elimination of HIV transmission, with an observed HIV incidence <0.5% per year compared to an expected incidence >5% per year. 25 Scale-Up of Preexposure Prophylaxis in San Francisco to Impact HIV Incidence Robert M. Grant 3 ; Albert Liu 2 ; Jen Hecht 4 ; Susan P. Buchbinder 2 ; ShannonWeber 1 ; Pierre-Cedric Crouch 4 ; Steven Gibson 4 ; Stephanie Cohen 2 ; David Glidden 1 1 University of California San Francisco (UCSF), San Francisco, CA, US; 2 San Francisco Department of Public Health, San Francisco, CA, US; 3 Gladstone Institutes, San Francisco, CA, US; 4 San Francisco AIDS Foundation, San Francisco, CA, US Background: Since 2007, rates of new HIV diagnoses in San Francisco (SF) decreased with widespread HIV testing, pooled HIV RNA testing for high-risk seronegatives, increased viral suppression rates, and grass-roots initiatives. Consumer demand for pre-exposure prophylaxis (PrEP) has increased since mid-2013. Local goals for PrEP scale-up have not been established. Methods: A simple model was developed to forecast HIV transmission with expanded PrEP use. The model considers infectiousness and partnering practices of diagnosed and undiagnosed persons with HIV infection, viral suppression rates, and transmission to uninfected people having low, moderate, or high numbers of partners. Model parameters for SF were derived from surveillance, local research on seroadaptive behaviors, and SF-specific data from cohort studies, including the iPrEx Open Label Extension (OLE). Adherence in OLE was monitored by drug concentrations in dried blood spots and mapped to efficacy using global iPrEx data. The optimistic scenario assumes PrEP uptake will attract and retain people with higher exposure to HIV, as was observed at SF’s OLE site. The realistic scenario assumes incidence rates that are typically observed in SF cohorts that did not include access to PrEP. Results: In SF, the HIV diagnosis rate is 94%with 67% viral suppression. Among 150 eligible participants in OLE in SF, 64% chose to start PrEP; People starting PrEP were more likely to report non-condom receptive anal intercourse (44% vs 26%; P=0.03). Adherence yielded substantially protective drug concentrations among 96% of users through week 24, falling slightly afterward. If PrEP were used by 6400 people in the optimistic scenario (incidence 1.3 to 4.2/100py), the number of new infections could fall by 50% city-wide; doubling the number on PrEP could reduce new infections to less than 50 per year, a 86% reduction. In the realistic scenario (incidence 0.8 to 2.5/100 py), the city-wide incidence falls by 30%with 6400 people on PrEP; getting to less than 50 cases a year requires that diagnosis rates increase to over 99%with 90% viral suppression, at which point PrEP’s impact on HIV incidence decreases because exposure to untreated HIV infection would be rare. Conclusions: Demand for PrEP is increasing in SF with high rates of adherence. Widespread use of PrEP could markedly decrease new HIV infections, especially if synergies between PrEP uptake and adherence, HIV exposure, and HIV testing continue during PrEP rollout. 26LB FACTS 001 Phase III Trial of Pericoital Tenofovir 1% Gel for HIV Prevention inWomen Helen Rees 1 ; Sinead A. Delany-Moretlwe 1 ; Carl Lombard 2 ; Deborah Baron 1 ; Ravindre Panchia 4 ; Landon Myer 3 ; Jill L. Schwartz 5 ; Gustavo F. Doncel 5 ; Glenda Gray 2 On behalf of the FACTS 001 StudyTeam 1 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa; 2 South African Medical Research Council, Cape Town, South Africa; 3 University of Cape Town, Cape Town, South Africa; 4 Perinatal HIV Research Unit, Soweto, South Africa; 5 CONRAD, Arlington, VA, US Background: HIV prevention in women is a major public health priority. Pericoital vaginal application of tenofovir (TFV) gel has been demonstrated to prevent male-to-female HIV transmission in a proof of concept phase IIB trial. However, adherence to product is a critical driver of microbicide effectiveness. Additional data are required for licensure. Methods: FACTS 001 is a phase III, multi-centre, double-blind, randomised, placebo-controlled trial undertaken in 9 sites in South Africa which evaluated the safety and effectiveness of pericoital TFV 1% gel when using the BAT-24 regimen (before and after sex; no more than 2 doses in 24h). HIV-negative women aged 18-30 years received intensive counselling on product adherence and HIV risk reduction with condom provision. Monthly follow-up visits included HIV and safety testing, return of unused product and used gel applicators, and ongoing counselling on product adherence for up to 27 months. Product adherence was measured by proportion of self-reported sex acts covered by gel. In the primary intent-to-treat analysis, the effectiveness of TFV gel was assessed using a log-rank test stratified by site. A nested case-cohort substudy (n=214) also examined TFV drug levels in quarterly cervicovaginal lavage (CVL) samples in HIV seroconverters vs controls. Results: Between Oct 2011 and Aug 2014, 3844 participants were screened, 2059 enrolled and 2029 included in the primary analysis. At enrolment, participant mean age was 23 years, most were unmarried (88%), lived with parents (62%), and had earned 〈 US$100 in the past 3 months (73%). 3036 person-years of observation were accrued and 7.4% of participants were lost to follow-up. Overall 123 HIV infections occurred (HIV incidence: 4.0/100 women years); 61 in the TFV arm and 62 in the placebo group (incidence rate

Oral Abstracts

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CROI 2015