Pharmacological measures of treatment adherence and risk of HIV infection in the VOICE study

James Y. Dai, Craig Hendrix, Barbra A. Richardson, Cliff Kelly, Mark A Marzinke, Z. Mike Chirenje, Jeanne M. Marrazzo, Elizabeth R. Brown

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)335-342
Number of pages8
JournalJournal of Infectious Diseases
Volume213
Issue number3
DOIs
StatePublished - Feb 1 2016

Fingerprint

Tenofovir
Virus Diseases
HIV
Pharmacology
Therapeutics
Gels
Proxy
Placebos

Keywords

  • causal inference
  • HIV prevention
  • preexposure prophylaxis
  • prevention efficacy
  • product adherence
  • tenofovir detection

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Pharmacological measures of treatment adherence and risk of HIV infection in the VOICE study. / Dai, James Y.; Hendrix, Craig; Richardson, Barbra A.; Kelly, Cliff; Marzinke, Mark A; Chirenje, Z. Mike; Marrazzo, Jeanne M.; Brown, Elizabeth R.

In: Journal of Infectious Diseases, Vol. 213, No. 3, 01.02.2016, p. 335-342.

Research output: Contribution to journalArticle

Dai, James Y. ; Hendrix, Craig ; Richardson, Barbra A. ; Kelly, Cliff ; Marzinke, Mark A ; Chirenje, Z. Mike ; Marrazzo, Jeanne M. ; Brown, Elizabeth R. / Pharmacological measures of treatment adherence and risk of HIV infection in the VOICE study. In: Journal of Infectious Diseases. 2016 ; Vol. 213, No. 3. pp. 335-342.
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