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Correlation Between Pill Counts and Biologic Effects in an HIV-1 Prevention Clinical Trial: Implications for Measuring Adherence

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Abstract

Clinic-based pill counts of unused study medication are frequently used to measure adherence in HIV-1 prevention trials. Monthly pill count adherence data from the Partners in Prevention HSV/HIV Transmission Study, a double-blind, placebo controlled trial of twice-daily acyclovir suppression of herpes simplex virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes between 3,381 placebo and active arm participants in two objective biologic measures of acyclovir’s drug activity: reduction in plasma HIV-1 RNA and HSV-2 genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data is strongly correlated with biological effects of adherence. However, when calculated adherence exceeded 102 % (i.e., fewer pills returned than expected) and when pill counts were missing because bottles were not returned, plasma HIV-1 RNA and GUD effects were diminished, likely indicating periods of non-adherence.

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Acknowledgments

We thank the couples who participated in this study, the teams at the study sites, particularly the pharmacy staff, and the team at the University of Washington International Clinical Research Center for their contributions to this study. The United States National Institutes of Health (Grant R01-MH095507) and the Bill and Melinda Gates Foundation (Grants #26469 and 41185).

Author information

Authors and Affiliations

  1. Department of Global Health, University of Washington, Seattle, WA, USA

    Deborah J. Donnell, Jared M. Baeten, Ting Hong, Jairam R. Lingappa, Andrew Mujugira, Edith Nakku-Joloba & Connie Celum

  2. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M2-200, Seattle, WA, 98109-1024, USA

    Deborah J. Donnell

  3. Department of Medicine, University of Washington, Seattle, WA, USA

    Jared M. Baeten, Jairam R. Lingappa & Connie Celum

  4. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Jared M. Baeten & Connie Celum

  5. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Jairam R. Lingappa

  6. Harvard Medical School, Boston, MA, USA

    David Bangsberg

  7. Massachusetts General Hospital, Boston, MA, USA

    David Bangsberg

Authors
  1. Deborah J. Donnell
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  2. Jared M. Baeten
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  3. Ting Hong
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  4. Jairam R. Lingappa
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  5. Andrew Mujugira
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  6. Edith Nakku-Joloba
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  7. David Bangsberg
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  8. Connie Celum
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Corresponding author

Correspondence to Deborah J. Donnell.

Additional information

This study was conducted on behalf of Partners in Prevention HSV/HIV Transmission Study Team (Members of the Partners in Prevention HSV/HIV Transmission Study Team listed in the Appendix section).

Appendix: Partners in Prevention HSV/HIV Transmission Study Team

Appendix: Partners in Prevention HSV/HIV Transmission Study Team

University of Washington Coordinating Center and Central Laboratories, Seattle, USA

Connie Celum (Principal Investigator), Anna Wald (Protocol Co-chair), Jairam Lingappa (Medical Director), Jared M. Baeten, Mary Campbell, Lawrence Corey, Robert W. Coombs, James P. Hughes, Amalia Magaret, M. Juliana McElrath, Rhoda Morrow, James I. Mullins.

Study Sites and Site Principal Investigators

Cape Town, South Africa (University of Cape Town): David Coetzee; Eldoret, Kenya (Moi University, Indiana University): Kenneth Fife, Edwin Were; Gaborone, Botswana (Botswana Harvard Partnership): Max Essex, Joseph Makhema; Kampala, Uganda (Infectious Disease Institute, Makerere University): Elly Katabira, Allan Ronald; Kigali, Rwanda (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, Kayitesi Kayitenkore, Etienne Karita; Kisumu, Kenya (Kenya Medical Research Institute, University of California San Francisco): Elizabeth Bukusi, Craig Cohen; Kitwe, Zambia (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, William Kanweka; Lusaka, Zambia (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, Bellington Vwalika; Moshi, Tanzania (Kilimanjaro Christian Medical College, Harvard University): Saidi Kapiga, Rachel Manongi; Nairobi, Kenya (University of Nairobi, University of Washington): Carey Farquhar, Grace John-Stewart, James Kiarie; Ndola, Zambia (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, Mubiana Inambao; Orange Farm, South Africa (Reproductive Health Research Unit, University of the Witwatersrand): Sinead Delany-Moretlwe, Helen Rees; Soweto, South Africa (Perinatal HIV Research Unit, University of the Witwatersrand): Guy de Bruyn, Glenda Gray, James McIntyre; Thika, Kenya (University of Nairobi, University of Washington): Nelly Rwamba Mugo.

Data management was provided by DF/Net Research, Inc. (Seattle, USA) and site laboratory oversight was provided by Contract Lab Services (University of the Witwatersrand, Johannesburg, South Africa).

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Donnell, D.J., Baeten, J.M., Hong, T. et al. Correlation Between Pill Counts and Biologic Effects in an HIV-1 Prevention Clinical Trial: Implications for Measuring Adherence. AIDS Behav 17, 632–639 (2013). https://doi.org/10.1007/s10461-012-0268-0

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