Current guidelines recommend 4 weeks of daily ARVs for post-exposure prophylaxis (PEP) after an HIV exposure, though the optimal duration of PEP is not known. An effective short-course regimen could simplify HIV prevention after an exposure, or provide an option for event-driven post-exposure prophylaxis (PrEP) as a simplified alternative to long-term daily regimen. Here, we evaluated PrEP/PEP regimens with Emtricitabine(FTC)/Tenofovir Alafenamide(TAF) combined with different doses of Bictegravir(BIC) in a non-human primate model of SHIV exposure.
A pharmacokinetic study was conducted in rhesus macaques with varying amounts of BIC + FTC/TAF (200/25 mg) to select BIC dose. Two efficacy studies were performed with 6 to 8 repeat low dose SHIV162P3 rectal challenges 2 weeks apart to minimize residual drug exposure. Two oral doses of ARVs were administered at different times relative to virus exposure. In Study 1, BIC/FTC/TAF (25/200/25mg) or FTC/TAF (200/25mg) was given at -2h/+24h (n=6), +24/+48h (n=6), or +48h/+72h (n=6 or 5). Follow-up Study 2 tested 100mg BIC in combination with FTC/TAF, (100/200/25mg) given at +6h/+30h, +12/+36h, +24h/+48h, +48h/+72h or FTC/TAF (200/25mg) at +6h/+30h or +12/+36h (n=6 each). A Kaplan-Meier survival analysis was conducted and a log-rank test was used to compare time to infection relative to placebo controls.
After 8 virus challenges in Study 1, BIC/FTC/TAF (25/200/25mg) protected 6/6 animals in the -2h/+24h group, 1/6 animals in the +24/+48h group and 0/6 animals in the +48/+72h group (Table 1). FTC/TAF alone protected 5/6 animals in the -2h/+24h group, 1/6 in the +24/+48h group and 0/5 in the +48/+72h group. After 6 virus challenges in Study 2, BIC/FTC/TAF (100/200/25mg) protected 5/6 animals in the +6h/+30h group, 6/6 animals in the +12/+36h, 4/6 animals in the +24h/+48h, and 3/6 animals in the +48h/+72h group (Table 1). In contrast, FTC/TAF (200/25mg) protected 3/6 animals in the +6h/+30h group and 4/6 animals in the +12/+36h group.
Two doses of FTC/TAF + BIC (100mg) initiated up to 24h after rectal virus exposure were protective in a SHIV/macaque model. FTC/TAF + BIC (25mg) provided similar protection to FTC/TAF alone and were only efficacious when used as -2/+24h regimen. These results provide support to further study FTC/TAF + BIC (100mg) as a simplified event-driven PEP regimen.