title: Disclosure of pharmacokinetic drug results to understand nonadherence.
abstract: OBJECTIVE
  In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE.
  
  
  METHODS
  We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1-74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed.
  
  
  RESULTS
  We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting.
  
  
  CONCLUSIONS
  Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.
authors.affiliation: aWomen's Global Health Imperative (WGHI), RTI International bCenter for AIDS Prevention Studies (CAPS), University of California, San Francisco, California, USA cUniversity of Zimbabwe-University of California San Francisco Collaborative Research Programme, Harare, Zimbabwe dMakerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda eHIV Prevention Research Unit, South African Medical Research Council, Durban, South Africa fFHI360, Durham, North Carolina, USA gDesmond Tutu HIV Centre, Department of Medicine, University of Cape Town, Cape Town, South Africa hNational Institute of Allergy and Infectious Diseases, Division of AIDS iNational Institute of Mental Health, Bethesda, Maryland jUniversity of Washington, Division of Allergy and Infectious Diseases, Seattle, Washington kPopulation Council, New York, New York, USA.
authors.forename: Ariane
authors.initials: A
authors.lastname: van der Straten
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Montgomery
authors.forename: Petina
authors.initials: P
authors.lastname: Musara
authors.forename: Juliane
authors.initials: J
authors.lastname: Etima
authors.forename: Sarita
authors.initials: S
authors.lastname: Naidoo
authors.forename: Nicole
authors.initials: N
authors.lastname: Laborde
authors.forename: Miriam
authors.initials: M
authors.lastname: Hartmann
authors.forename: Lisa
authors.initials: L
authors.lastname: Levy
authors.forename: Thola
authors.initials: T
authors.lastname: Bennie
authors.forename: Helen
authors.initials: H
authors.lastname: Cheng
authors.forename: Jeanna
authors.initials: J
authors.lastname: Piper
authors.forename: Cynthia I
authors.initials: CI
authors.lastname: Grossman
authors.forename: Jeanne
authors.initials: J
authors.lastname: Marrazzo
authors.forename: Barbara
authors.initials: B
authors.lastname: Mensch
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D055118:Medication Adherence; D010949:Plasma / Q000737:chemistry*; D012189:Retrospective Studies; D013019:South Africa; D000068698:Tenofovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014454:Uganda; D055815:Young Adult; D015030:Zimbabwe
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir