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Pre-exposure prophylaxis (PrEP) with a weekly oral regimen of antiretroviral drugs could be a suitable preventative option for individuals who struggle with daily PrEP or prefer not to use long-acting injectables. We assessed in macaques the efficacy of weekly oral tenofovir alafenamide (TAF) at doses of 13.7 or 27.4 mg/kg. Macaques received weekly oral TAF for six weeks and were exposed twice-weekly to SHIV vaginally or rectally on day 3 and 6 after each dose. Median TFV-DP levels in PBMCs following the 13.7 mg/kg dose were 3110 and 1137 fmols/106 cells on day 3 and 6, respectively. With the 27.4 mg/kg dose, TFV-DP levels were increased (~2-fold) on day 3 and 6 (6095 and 3290 fmols/106 cells, respectively). Both TAF doses (13.7 and 27.4 mg/kg) conferred high efficacy (94.1% and 93.9%, respectively) against vaginal SHIV infection. Efficacy of the 27.4 mg/kg dose against rectal SHIV infection was 80.7%. We estimate that macaque doses of 13.7 and 27.4 mg/kg are equivalent to approximately 230 and 450 mg of TAF in humans, respectively. Our findings demonstrate the effectiveness of a weekly oral PrEP regimen and suggest that a clinically achievable oral TAF dose could be a promising option for non-daily PrEP. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy (HAART) has been successful in reducing HIV-1-associated morbidity and mortality since its introduction in 1996. It, however, fails to eradicate HIV-1 infection thoroughly. The high cost of life-long HAART and the emergence of drug resistance among HIV-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. Traditional Chinese medicine (TCM) is one of the mainstreams of complementary and alternative medicine, and serves as rich resources for new drug development. Despite almost 100 plant-derived compounds are in clinical trials, few target HIV-1 infection. In this study, we discovered that extract of Sanguisorba officinalis (SOE) has anti-HIV-1 activities. Using a cell-based assay and single-cycle luciferase reporter viruses pseudotyped with envelopes from HIV-1 or control viruses, we found that SOE exhibited significant inhibitory ability against both CCR5 and CXCR4 tropic HIV-1 (ADA and HXB2) with respective IC 50 values of 1.91±0.16 μg/ml and 3.70±0.53 μg/ml. Interestingly, SOE also inhibited SIV infection but failed to block vesicular stomatitis virus (VSV), SARS-CoV and influeunza H5N1 pseudoviruses. Furthermore, we showed that SOE had no effects on post-entry events of HIV-1 replication. It blocked entry by acting on viral envelope directly because SOE pre-treatment with the virus but not with cell lines expressing viral receptors showed the maximal inhibitory activity. In addition, SOE was able to inhibit reverse-transcription-inhibitor-resistant viruses (K103N, Y188L, and K103N/Y188L/G190A) and a protease-inhibitor-resistant strain (PI-2840). Our findings demonstrated SOE as a novel and specific entry inhibitor, which shed lights on the discovery of anti-HIV-1 drugs from traditional herbal medicines.