title: Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN-003 (VOICE) study.
abstract: BACKGROUND
  In the Microbicide Trial Network MTN-003 (VOICE) study, a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir (TFV), product adherence was poor based on pharmacokinetic (PK) drug detection in a random subsample. Here, we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting.
  
  
  METHODS
  We included participants with PK and behavioural data from VOICE random subsample. Behavioural assessments included face-to-face interviews (FTFI), audio computer-assisted self-interviewing (ACASI) and pharmacy-returned product counts (PC). TFV concentrations < 0.31 ng/mL in plasma (oral group) and < 8.5 ng/swab in vaginal group were defined as "PK non-adherent." Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve (AUC). Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model.
  
  
  RESULTS
  In this random adherence cohort of VOICE participants assigned to active products, (N = 472), PK non-adherence was 69% in the oral group (N = 314) and 65% in the vaginal group (N = 158). Behaviourally, ≤ 10% of the cohort reported low/none use with any behavioural measure and accuracy was low (≤ 43%). None of the regression models had an AUC > 0.65 for any single or combined behavioural measures. Significant (p < 0.05) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group; whereas for the vaginal group, being somewhat worried about HIV was associated with lower risk of over-reporting.
  
  
  CONCLUSIONS
  PK measures indicated similarly low adherence for the oral and vaginal groups. No behavioural measure accurately predicted PK non-adherence. Accurate real-time measures to monitor product adherence are urgently needed.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00705679.
authors: Women's Global Health Imperative (WGHI) RTI International, San Francisco, CA, USA.|Center for AIDS Prevention Studies (CAPS), Department of Medicine, University of California San Francisco, San Francisco, CA, USA; ariane@rti.org.
authors: Ariane
authors: A
authors: van der Straten
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Departments of medicine and of biostatistics, University of Washington Seattle, WA, USA.
authors: Elizabeth R
authors: ER
authors: Brown
authors: Departments of medicine and of biostatistics, University of Washington Seattle, WA, USA.
authors: Jeanne M
authors: JM
authors: Marrazzo
authors: University of Zimbabwe-UCSF Research Collaboration, Harare, Zimbabwe.
authors: Michael Z
authors: MZ
authors: Chirenje
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Karen
authors: K
authors: Liu
authors: FHI360, Durham, NC, USA.
authors: Kailazarid
authors: K
authors: Gomez
authors: Department of medicine, Johns Hopkins University, Baltimore, MD, USA.
authors: Mark A
authors: MA
authors: Marzinke
authors: NIAID/DAIDS Bethesda, MD, USA.
authors: Jeanna M
authors: JM
authors: Piper
authors: Department of medicine, Johns Hopkins University, Baltimore, MD, USA.
authors: Craig W
authors: CW
authors: Hendrix
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D016015:Logistic Models; D055118:Medication Adherence; D065129:Pre-Exposure Prophylaxis; D000068698:Tenofovir / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir
keywords: HIV; adherence measurement; microbicide; pharmacokinetic drug detection; pre-exposure prophylaxis