Pharmacological Measures of Treatment Adherence and Risk of HIV Infection in the VOICE Study
Year: 2015
Type: article
Abstract: BACKGROUND: None of the 3 regimens tested in the VOICE study showed protection against human immunodeficiency virus (HIV) infection in intent-to-treat analyses. Plasma tenofovir concentrations demonstrated poor adherence to the study product among study subjects. Statistical analyses to explore the causal treatment effect on the prevention of HIV infection among adherent individuals are needed. METHODS: We developed an analytical strategy to evaluate whether conventional covariate adjustment removes confounding and thereby reveals a prevention effect among adherent individuals. We applied this strategy to the VOICE study, using 2 dichotomized proxy measures of product use: detection of tenofovir in plasma at least once during follow-up and detection of tenofovir in plasma at the 3-month follow-up visit. RESULTS: After adjustment for a set of baseline predictors of the risk of HIV transmission, the confounding associated with comparison of adherent individuals in the tenofovir gel arm to placebo recipients was nearly eliminated. The relative risk for a prevention effect among those ever having tenofovir detected was 0.53 (P = .038); the relative risk among those having tenofovir detected at 3 months was 0.40 (P = .045). CONCLUSIONS: A novel regression approach was proposed for causal as-treated analyses in the VOICE study. While intent-to-treat analyses yield null results, this exploratory approach presented evidence suggesting a prevention effect among gel users. CLINICAL TRIALS REGISTRATION: NCT00705679.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Gilead Sciences, National Institutes of Health, National Institute of Mental Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1309410973, G1999867236, Leadership for HIV/AIDS Clinical Trials Networks; Microbicide Trials Network, Statistical and Data Management Center (SDMC): Microbicide Trials Network, Leadership and Operations Center (LOC): Microbicide Trials Network, G3458544401, G533257933, G628764967, Laboratory Center (LC): Microbicide Trials Network, Statistical Issues in AIDS Research, G9000107377, The Johns Hopkins Center for AIDS Research (JHU CFAR), Cancer Center Support Grant, Statistical Issues in AIDS Research
OpenAlex ID: W1917043471