AIDS and Behavior

, Volume 20, Issue 11, pp 2654–2661 | Cite as

Reporting of Adherence in the VOICE Trial: Did Disclosure of Product Nonuse Increase at the Termination Visit?

  • Barbara S. MenschEmail author
  • Elizabeth R. Brown
  • Karen Liu
  • Jeanne Marrazzo
  • Zvavahera Mike Chirenje
  • Kailazarid Gomez
  • Jeanna Piper
  • Karen Patterson
  • Ariane van der Straten
Original Paper


VOICE—a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe—found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, ≥90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report.


Microbicide trials Self-reports of adherence sub-Saharan Africa 



We thank the study participants as well as the VOICE Study team members who implemented the trial. We also thank Elizabeth Montgomery for comments on an earlier draft.


The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


  1. 1.
    Coly A, Gorbach PM. Microbicide acceptability research: recent findings and evolution across phases of product development. Curr Opin HIV AIDS. 2008;3(5):581–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Mensch BS, van der Straten A, Katzen LL. Acceptability in microbicide and PrEP Trials: current status and a reconceptualization. Curr Opin HIV AIDS. 2012;7(6):534–41.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Skoler-Karpoff S, Ramjee G, Ahmed K, et al. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9654):1977–87.CrossRefPubMedGoogle Scholar
  4. 4.
    Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367(5):411–22.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Trussell J, Dominik R. Will microbicide trials yield unbiased estimates of microbicide efficacy? Contraception. 2005;72(6):408–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Masse BR, Boily MC, Dimitrov D, Desai K. Efficacy dilution in randomized placebo-controlled vaginal microbicide trials. Emerg Themes Epidemiol. 2009;6:5.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rees H, Delany-Moretlwe S, Baron D, et al. FACTS 001 phase III trial of pericoital tenofovir 1 % gel for HIV prevention in women. Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015. p. 23–26Google Scholar
  8. 8.
    Gorbach P, Mensch BS, Husnik M, et al. Effect of computer-assisted interviewing on self-reported sexual behavior data in a microbicide clinical trial. AIDS Behav. 2013;17(2):790–800.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mensch BS, Hewett PC, Abbott S, et al. Assessing the reporting of adherence and sexual activity in a simulated microbicide trial in South Africa: an interview mode experiment using a placebo gel. AIDS Behav. 2011;15(2):407–21.CrossRefPubMedGoogle Scholar
  10. 10.
    Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6):509–18.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Abbott SA, Friedland BA, Sarna A, et al. An evaluation of methods to improve the reporting of adherence in a placebo gel trial in Andhra Pradesh, India. AIDS Behav. 2013;17(6):2222–36.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    van der Straten A, Montgomery ET, Hartmann M, Minnis A. Methodological lessons from clinical trials and the future of microbicide research. Curr HIV/AIDS Rep. 2012;10(1):89–102.CrossRefGoogle Scholar
  13. 13.
    Servick K. ‘Nonadherence’: a bitter pill for drug trials. Science. 2014;346(6207):288–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Lu M, Safren SA, Skolnik PR, et al. Optimal recall period and response task for self-reported HIV medication adherence. AIDS Behav. 2008;12(1):86–94.CrossRefPubMedGoogle Scholar
  15. 15.
    Feldman BJ, Fredericksen RJ, Crane PK, et al. Evaluation of the single-item self-rating adherence scale for use in routine clinical care of people living with HIV. AIDS Behav. 2013;17(1):307–18.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    van der Straten A, Mayo A, Brown ER, et al. Perceptions and experiences with the VOICE Adherence Strengthening Program (VASP) in the MTN-003 trial. AIDS Behav. 2015;19(5):770–83.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Musara P, Munaiwa O, Mahaka I, et al. The effect of presentation of pharmacokinetic (PK) drug results on self-reported study product adherence among VOICE participants in Zimbabwe. HIV Research for Prevention Conference, Cape Town; 2014.Google Scholar
  18. 18.
    Corneli AL, McKenna K, Perry B, et al. The science of being a study participant: FEM-PrEP participants’ explanations for overreporting adherence to the study pills and for the whereabouts of unused pills. J Acquir Immune Defic Syndr. 2015;68(5):578–84.CrossRefPubMedGoogle Scholar
  19. 19.
    van der Straten A, Montgomery ET, Musara P, et al. Disclosure of pharmacokinetic drug results to understand nonadherence. AIDS. 2015;29(16):2161–71.CrossRefPubMedGoogle Scholar
  20. 20.
    Minnis AM, van der Straten A, Salee P, Hendrix CW. Pre-exposure prophylaxis adherence measured by plasma drug level in MTN-001: comparison between vaginal gel and oral tablets in two geographic regions. AIDS Behav. 2015;. doi: 10.1007/s10461-015-1081-3.Google Scholar
  21. 21.
    van der Straten A, Stadler J, Luecke E, et al. Perspectives on use of oral and vaginal antiretrovirals for HIV prevention: the VOICE-C qualitative study in Johannesburg, South Africa. J Int AIDS Soc. 2014;17(Suppl 2):19146.PubMedPubMedCentralGoogle Scholar
  22. 22.
    van der Straten A, Stadler J, Montgomery E, et al. Women’s experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa. PLoS One. 2014;9(2):e89118.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Barbara S. Mensch
    • 1
    Email author
  • Elizabeth R. Brown
    • 2
    • 3
  • Karen Liu
    • 3
  • Jeanne Marrazzo
    • 2
  • Zvavahera Mike Chirenje
    • 4
  • Kailazarid Gomez
    • 5
  • Jeanna Piper
    • 6
  • Karen Patterson
    • 3
  • Ariane van der Straten
    • 7
  1. 1.Population CouncilNew YorkUSA
  2. 2.University of WashingtonSeattleUSA
  4. 4.UZ-UCSF Collaborative Research ProgrammeHarareZimbabwe
  5. 5.FHI360DurhamUSA
  6. 6.National Institute of Allergy and Infectious Diseases/DAIDSRockvilleUSA
  7. 7.Women’s Global Health ImperativeRTI InternationalSan FranciscoUSA

Personalised recommendations