CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Methods: We expanded our network-based mathematical model of HIV among MSM to include transmission of rectal and urethral Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT). PrEP use was simulated following the behavioral indications and ongoing HIV/STI screening recommendations in the CDC PrEP guidelines. Model scenarios varied PrEP coverage (the proportion of MSM indicated for PrEP who received it), the STI screening interval, and RC level (the reduction in the probability of condom use within partnerships). Results: Under 20% PrEP coverage, the recommended biannual STI screening, and no risk compensation, an estimated 27.5% of GC infections and 31.2% of CT infections would be averted over the next decade. This occurred because PrEP-related STI screening resulted in a 2.1-fold and 2.8-fold increase in the treatment of rectal GC and CT, respectively. Screening at every 3 months (vs 6 months) would avert 33.9% of GC and 35.9% of CT. Doubling PrEP coverage to 40% (with biannual screening) would avert about half of GC and CT infections. At 50% RC (with 20% PrEP coverage & biannual STI screening), the incidence rates of GC and CT would be 1.6 and 1.5 times higher compared to 0% RC. Conclusion: Implementation of the CDC clinical practice guidelines for PrEP may serve as a high-impact STI prevention intervention due to the salutary effects of the recommended STI screening schedule. The bio-behavioral indications for PrEP could also be well-suited to identify MSM at substantial risk of STI infections that would otherwise remain undiagnosed, including asymptomatic rectal GC and CT. Reducing the STI screening interval to quarterly may not be efficient, as this doubling of STI testing and treatment only reduces population-level STI incidence by a further 5–6%. RC increases STI incidence, but is unlikely to offset the STI prevention benefits of adherence to PrEP-related STI screening recommendations. 1035 ANTICIPATED ADHERENCE, EFFICACY, AND IMPACT OF WEEKLY ORAL PREEXPOSURE PROPHYLAXIS Christian Selinger 1 , Ameya Kirtane 2 , Omar Abouzid 2 , Robert Langer 2 , Carlo G. Traverso 3 , Anna Bershteyn 1 1 Inst for Disease Modeling, Bellevue, WA, USA, 2 Massachusetts Inst of Tech, Cambridge, MA, USA, 3 Brigham and Women’s Hosp, Boston, MA, USA Background: Advances in drug delivery will soon make week-long orally delivered controlled release of highly potent anti-retroviral drugs a possibility. We estimated the potential impact of developing these technologies into a weekly oral pre-exposure prophylaxis (PrEP) formulation as an alternative to presently available daily oral PrEP. Methods: To estimate the most likely impact of weekly PrEP on efficacy, we performed a meta-analysis of the difference in adherence (defined as medication possession ratio (MPR)>80%) to preventative drugs for chronic medical conditions. The relationship between plasma drug concentration and medication possession was estimated based on measurements in the Partners PrEP Study. The relationship between plasma drug concentration of tenofovir disoproxil fumarate and PrEP efficacy was estimated from the VOICE, FEM-PrEP, iPrEx, iPrEx-OLE, Partners PrEP, and Partners Demonstration Studies. The population-level impact of weekly vs. daily oral PrEP on infections averted in South Africa was simulated using the microsimulation model EMOD-HIV v2.5. We assumed 30% baseline PrEP coverage and 50% baseline PrEP efficacy, and varied the increment in efficacy and coverage for weekly compared to daily formulations. Results: Random effects meta-analysis estimated that weekly dosage forms were associated with a 9% (CI: 5%-13%) greater MPR than daily dosage for the same medical condition. When adherence is high, MPR is similar to pill count, and the latter had 84% sensitivity to identify individuals with detectable tenofovir in blood while taking daily oral PrEP. One percentage increase in fraction with detectable drug levels was associated with a 1.5% increase in efficacy of oral PrEP across studies. Taken together, this suggests that weekly formulation could increase PrEP efficacy by 12% (CI: 6%-17%). Modeling suggests that weekly PrEP could avert 200,000 to 800,000 additional infections over twenty years in South Africa (Figure). This range of uncertainty reflects uncertainty in the true impact of weekly PrEP formulation on efficacy, whether there is also a difference in coverage due to acceptability of weekly PrEP, and concurrent ART scale-up. Conclusion: Weekly oral PrEP has the potential to substantially increase PrEP efficacy and population-level impact relative to daily oral PrEP. Drug potency and sustained delivery mechanisms should be a high priority in oral PrEP development.

Poster and Themed Discussion Abstracts

1036 POPULATION-LEVEL IMPACT AND COST-EFFECTIVENESS OF AN HIV VACCINE IN SOUTH AFRICA Christian Selinger 1 , Anna Bershteyn 1 , Dobromir Dimitrov 2 , Timothy B. Hallett 3 , Linda-Gail Bekker 4 , Helen Rees 5 , Glenda Gray 6 , for the Pox-Protein Public-Private Partnership Global Access Committee 1 Inst for Disease Modeling, Bellevue, WA, USA, 2 Fred Hutchinson Cancer Rsr Cntr, Seattle, WA, USA, 3 Imperial Coll London, London, UK, 4 Univ of Cape Town, Cape Town, South Africa, 5 Wits Reproductive Hlth and HIV Inst, Johannesburg, South Africa, 6 Perinatal HIV Rsr Unit, Soweto, South Africa Background: The RV144 trial is to date the only demonstration of a partially effective HIV vaccine. Preliminary results from HVTN100 suggest similar immunogenicity for an ALVAC HIV clade C vaccine. Efficacy studies of ALVAC clade C with gp120 will include an additional booster at 12 months. Here, the population-level impact and maximum acceptable price of such a vaccine in South Africa are explored using EMOD, an individual-based network model.

CROI 2017 447