Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection
Ivana Massud,
Kenji Nishiura,
Susan Ruone,
Angela Holder,
Chuong Dinh,
Jonathan Lipscomb,
James Mitchell,
George M. Khalil,
Walid Heneine,
J. Gerardo Garcίa-Lerma,
Charles W. Dobard
Affiliations
Ivana Massud
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Kenji Nishiura
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Susan Ruone
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Angela Holder
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Chuong Dinh
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Jonathan Lipscomb
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
James Mitchell
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
George M. Khalil
Quantitative Sciences and Data Management Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
Walid Heneine
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
J. Gerardo Garcίa-Lerma
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Charles W. Dobard
Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
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.
