Advertisement

Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE

  • Barbara S. Mensch
  • Barbra A. Richardson
  • Marla Husnik
  • Elizabeth R. Brown
  • Flavia Matovu Kiweewa
  • Ashley J. Mayo
  • Jared M. Baeten
  • Thesla Palanee-Phillips
  • Ariane van der Straten
  • for the MTN-020/ASPIRE study team
Original Paper
  • 26 Downloads

Abstract

This analysis compares self-reports of product use with objective measures of non-adherence—quarterly plasma dapivirine levels and monthly residual dapivirine (DPV) levels in used rings—in MTN-020/ASPIRE, a phase 3 trial of a monthly DPV vaginal ring among women aged 18–45 years in Malawi, South Africa, Uganda and Zimbabwe. For participants on active product (N = 1211) we assessed self-reported monthly non-adherence, as measured by (1) whether the ring was ever out, and out for ≥ 12 h in the previous month and, (2) by a self-rating scale assessing ability to keep the vaginal ring inserted, and compared the self-reports to two biomarkers of non-use separately and as a composite measure. For this analysis, a plasma DPV value ≤ 95 pg/ml and residual ring ≥ 23.5 mg were used to classify non-adherence (i.e. the ring never being in the vagina the previous month). Compared to self-reports, non-adherence was found to be substantially higher for the composite measure as well as its two components, an indication that ring removal was likely underreported in the trial. The discrepancy between the self-report measure of ring outage and the composite indicator was greater for those aged 18–21 than for those older, evidence that younger women are more likely to underreport non-adherence. Despite underreporting of non-adherence, self-reports of the ring never being out were significant in predicting the composite objective measure. Furthermore, the association between the self-rating scale and the objective measure was in the expected direction and significant, although 11% of those 18–21 and 7% of those 22+ who rated their ability to keep the ring inserted as good, very good or excellent in the 4 weeks prior to exit were considered non-adherent according to the objective measure. This analysis indicates that while self-reports are significantly associated with objective measures of adherence in the ASPIRE trial, they were inflated—more so by those younger—and therefore may have limited utility identifying those who have challenges using products as directed. ClinicalTrials.gov number NCT01617096

Keywords

Microbicides HIV prevention Non-adherence Self-reports Objective measures Vaginal ring Sub-Saharan Africa 

Notes

Acknowledgements

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. We thank the study participants as well as the ASPIRE Study team members who implemented the trial.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical Approval

The ASPIRE trial protocol was approved by the ethics review committee at each site.

Informed Consent

All participants provided written informed consent.

References

  1. 1.
    Kharsany AB, Karim QA. HIV infection and AIDS in Sub-Saharan Africa: current status, challenges and opportunities. Open AIDS J. 2016;10:34.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    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
  3. 3.
    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
  4. 4.
    Tolley EE, Harrison PF, Goetghebeur E, et al. Adherence and its measurement in phase 2/3 microbicide trials. AIDS Behav. 2010;14(5):1124–36.CrossRefPubMedGoogle Scholar
  5. 5.
    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
  6. 6.
    Montgomery ET, Mensch B, Musara P, et al. Misreporting of product adherence in the MTN-003/VOICE trial for HIV prevention in Africa: participants’ explanations for dishonesty. AIDS Behav. 2017;21(2):481–91.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Thurman AR, Clark MR, Hurlburt JA, Doncel GF. Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies. Int J Women’s Health. 2013;5:695–708.CrossRefGoogle Scholar
  8. 8.
    Nel A, Haazen W, Nuttall J, Romano J, Rosenberg Z, van Niekerk N. A safety and pharmacokinetic trial assessing delivery of dapivirine from a vaginal ring in healthy women. AIDS. 2014;28(10):1479–87.CrossRefPubMedGoogle Scholar
  9. 9.
    Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. 2016;375(22):2121–32.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Stalter RM, Moench TR, MacQueen KM, Tolley EE, Owen DH. Biomarkers and biometric measures of adherence to use of ARV-based vaginal rings. J Int AIDS Soc. 2016;19(1):20746.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    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
  12. 12.
    van der Straten A, Brown ER, Marrazzo JM, et al. Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN-003 (VOICE) study. J Int AIDS Soc. 2016;19(1):206426.Google Scholar
  13. 13.
    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
  14. 14.
    Minnis AM, et al. Adherence and acceptability in MTN 001: a randomized cross-over trial of daily oral and topical tenofovir for HIV prevention in women. AIDS Behav. 2013;17(2):737–47.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mensch BS, Brown ER, Liu K, et al. Reporting of adherence in the VOICE trial: did disclosure of product nonuse increase at the termination visit? AIDS Behav. 2016;20(11):2654–61.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mensch BS, Hewett PC, Erulkar AS. The reporting of sensitive behavior by adolescents: a methodological experiment in Kenya. Demography. 2003;40(2):247–68.CrossRefPubMedGoogle Scholar
  17. 17.
    Kelly CA, Hewett PC, Mensch BS, et al. Using biomarkers to assess the validity of sexual behavior reporting across interview modes among young women in Kampala, Uganda. Stud Fam Plan. 2014;45(1):43–58.CrossRefGoogle Scholar
  18. 18.
    Nnko S, Boerma JT, Urassa M, Mwaluko G, Zaba B. Secretive females or swaggering males? An assessment of the quality of sexual partnership reporting in rural Tanzania. Soc Sci Med. 2004;59(2):299–310.CrossRefPubMedGoogle Scholar
  19. 19.
    Plummer ML, Ross DA, Wight D, et al. A bit more truthful: the validity of adolescent sexual behavior data collected in rural northern Tanzania using five methods. Sex Transm Infect. 2004;80:ii49–56.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zaba B, Pisani E, Slaymaker E, Boerma JT. Age at first sex: understanding recent trends in African demographic surveys. Sex Transm Infect. 2004;80:ii28–35.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Barbara S. Mensch
    • 1
  • Barbra A. Richardson
    • 2
    • 3
  • Marla Husnik
    • 4
  • Elizabeth R. Brown
    • 2
    • 3
  • Flavia Matovu Kiweewa
    • 5
  • Ashley J. Mayo
    • 6
  • Jared M. Baeten
    • 2
  • Thesla Palanee-Phillips
    • 7
  • Ariane van der Straten
    • 8
    • 9
  • for the MTN-020/ASPIRE study team
  1. 1.Population CouncilNew YorkUSA
  2. 2.Department of BiostatisticsUniversity of WashingtonSeattleUSA
  3. 3.Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  4. 4.SCHARP-Fred Hutchinson Cancer Research CenterSeattleUSA
  5. 5.Makerere University-Johns Hopkins University Research CollaborationKampalaUganda
  6. 6.FHI360DurhamUSA
  7. 7.Wits Reproductive Health and HIV InstituteUniversity of the WitwatersrandJohannesburgSouth Africa
  8. 8.Women’s Global Health Imperative, RTI InternationalSan FranciscoUSA
  9. 9.Department of MedicineUniversity of California San FranciscoSan FranciscoUSA

Personalised recommendations