학술논문
Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.
Document Type
Academic Journal
Author
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.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101534003 Publication Model: Electronic Cited Medium: Print ISSN: 1999-4923 (Print) Linking ISSN: 19994923 NLM ISO Abbreviation: Pharmaceutics Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1999-4923
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/10 6 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/10 6 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.