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Efficacy of on-demand PrEP or PEP with single oral doses of combination
tenofovir alafenamide, emtricitabine, elvitegravir, and cobicistat in macaques
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Reported by Jules Levin
IAS 2019 July 21-25 Mexico City
Ivana Massud1, Susan Ruone1, Maria Zlotorzynska2, Richard Haaland1, Mian-er Cong1, Kristen Kelley1, Ryan Johnson1, Angela
Holder1, Chuong Dinh1, George Khalil1, Yi Pan1, Colleen Kelley3, Travis Sanchez2, Walid Heneine1, J. Gerardo García-Lerma1
1Centers for Disease Control and Prevention, Atlanta, GA.
2Rollins School of Public Health, Emory University, Atlanta, GA
3Emory University School of Medicine, Emory University, Atlanta, GA
Background: Coitally timed antiretroviral dosing for HIV prevention ("on-demand" PrEP or PEP) may be preferred and cost-effective. Here, we investigated if single oral doses of combination TAF/FTC/EVG/c can prevent rectal SHIV infection in macaques. We also compared human and macaque rectal tissue pharmacokinetics, and assessed willingness to use on-demand PrEP or PEP among men who have sex with men (MSM).
Methods: Efficacy of TAF/FTC/EVG/c was investigated in macaques exposed rectally to SHIV once a week for up to 8 weeks and treated at different times before or after exposure: -24h (n=6), -4h (n=6), +2h (n=5), +6h (n=6), and +24h (n=6). Infection outcome was compared to untreated controls. Drug levels in rectal tissues were compared between macaques and HIV-negative MSM (n=7) receiving a single fixed-dose combination TAF/FTC/EVG/c tablet. A national online HIV behavioral surveillance survey of MSM (N=1668) in the US assessed willingness to use on-demand PrEP or PEP. Participants were randomized to receive one of five questions: daily PrEP, PrEP (-24h or -2h) or PEP (+2h or +24h).
Results: Efficacy of single dose TAF/FTC/EVG/c was 80%[10.8-95.5] in the -24h group, 91.7%[35.7-98.9] in the -4h, 100% in the +2h, 80.1%[13.9-95.4] in the +6h, and 64.6%[-19.4,89.5] in the +24h group. After a single dose, median TFV-DP levels in rectal tissues at 24h were similar in macaques and humans (p>0.5); FTC-TP was mostly undetectable. Tissue EVG, FTC, and TFV in macaques and humans were also similar (p>0.5 for all comparisons). Willingness to use on-demand PrEP/PEP was highest for PEP 24h after sex and lowest for PrEP 24h before sex among both current PrEP users (83.9% vs 52.2%, p< 0.0001) and non-PrEP users (83.3% vs 70.0%, p< 0.0001). Among PrEP non-users, willingness to use any form of on-demand PrEP or PEP (+2h or +24h) was higher than to use daily PrEP (77.6% vs 57.2%, p< 0.0001).
Conclusions: A single oral dose of TAF/FTC/EVG/c around the time of exposure protected macaques from rectal SHIV infection. The highest efficacy was seen when animals were dosed shortly before or after exposure. The high efficacy and willingness to use on-demand PrEP or PEP among MSM support the clinical development of this intervention.
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