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Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.
Massud, Ivana; Nishiura, Kenji; Ruone, Susan; Holder, Angela; Dinh, Chuong; Lipscomb, Jonathan; Mitchell, James; Khalil, George M; Heneine, Walid; Garcia-Lerma, J Gerardo; Dobard, Charles W.
Afiliación
  • Massud I; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Nishiura K; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Ruone S; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Holder A; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Dinh C; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Lipscomb J; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Mitchell J; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Khalil GM; 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.
  • Heneine W; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Garcia-Lerma JG; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
  • Dobard CW; Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Pharmaceutics ; 16(3)2024 03 11.
Article en En | MEDLINE | ID: mdl-38543278
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza