Genital tenofovir concentrations correlate with protection against HIV infection in the CAPRISA 004 trial: Importance of adherence for microbicide effectiveness
Published Date:Jul 1 2015
Source:J Acquir Immune Defic Syndr. 69(3):264-269.
Pubmed Central ID:PMC4505741
Funding:D43 TW000231/TW/FIC NIH HHS/United States
D43TW00231/TW/FIC NIH HHS/United States
P30 AI050410/AI/NIAID NIH HHS/United States
P30 AI50410/AI/NIAID NIH HHS/United States
R34 AI087065/AI/NIAID NIH HHS/United States
U01 AI048008/AI/NIAID NIH HHS/United States
U01 AI069469/AI/NIAID NIH HHS/United States
U01 AI095031/AI/NIAID NIH HHS/United States
U2G PS001350/PS/NCHHSTP CDC HHS/United States
UM1 AI069469/AI/NIAID NIH HHS/United States
The CAPRISA 004 trial showed that coitally-dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protection against HIV acquisition.
Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared to 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total, 336 cervicovaginal fluid (CVF), 55 plasma, and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection.
Tenofovir was detected in the genital tract in 8(23.5%) cases and 119(39.4%) controls (p=0.076). Among those with detectable genital tract tenofovir, the median CVF concentrations were 97% lower in cases compared to controls, 476ng/ml versus 13821ng/ml (p=0.107). A total of 14.7% (5/34) of cases and 32.8 % (99/302) of controls were found to have tenofovir CVF concentrations above 100ng/mL (Odds Ratio (OR): 0.35, p=0.037). At a higher threshold, 8.8 %(3/34) of cases and 26.2 % (79/302) of controls were found to have tenofovir CVF concentrations above 1000ng/mL (OR: 0.27, p=0.036). Plasma tenofovir concentrations were <1ng/mL in all women and were less frequently detected in cases (0%) than controls (16.7 %) (p=0.031). Returned used tenofovir gel applicators and CVF concentrations were correlated (Spearman r=0.22, p=0.001).
A tenofovir concentration of ≥100ng/mL in CVF was associated with 65% (CI: 6%; 87%) protection against HIV, while a ≥1000ng/mL concentration correlated with 76% (CI: 8%; 92%) protection against HIV infection.
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