Skip to main content

Sexual behavior and medication adherence in men who have sex with men participating in a pre-exposure prophylaxis study of combinations of Maraviroc, Tenofovir Disoproxil Fumarate and/or Emtricitabine (HPTN 069/ACTG 5305)

AIDS and Behavior volume 26, pages 4107–4114 (2022)Cite this article

Abstract

HPTN 069/ACTG 5305 was designed to evaluate potential new PrEP regimens that included maraviroc, tenofovir disoproxil fumarate, and/or emtricitabine. The current analyses assessed antiretroviral (ARV) plasma concentrations in relation to sexual behavior in 224 cisgender men who have sex with men and 2 transgender women at risk for HIV. Poisson generalized estimating equations (GEE) regression were used to test for associations between self-reported sexual behavior, sociodemographic, behavioral variables, and study drug levels The median (IQR) age was 30 [25, 37] years old; 48.2% had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, one third of participants reported condomless anal sex (CAS) in the prior month with more than one partner. CAS was associated with daily ARV drug use (χ2 = 12.64, p = 0.002). Older individuals and those with greater education were more likely to ingest ARV drugs daily (χ2 = 9.36, p = 0.009 and χ2 = 8.63, p = 0.013, respectively), while neither race nor ethnicity was associated with daily ARV drug use. Participants who reported recent condomless anal sex and/or advanced education had higher rates of daily ARV drug use. These data support the need for ongoing adherence counseling in clinical trials of new PrEP modalities.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Data Availability

De-identified data sets can be made available upon request.

Code Availability

De-identified data can be made available upon request.

References

  1. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387:53–60.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Molina JM, Capitant C, Spire B, et al. On-demand pre-exposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373:2237–46.

    Article  CAS  PubMed  Google Scholar 

  4. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–34.

    Article  CAS  PubMed  Google Scholar 

  6. US Centers for Disease Control and Prevention. Recommendations for HIV prevention for adults and adolescents with HIV in the United States. Available at: https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf. Accessed October 16, 2021.

  7. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. 2021. Available at: https://www.who.int/publications/i/item/9789240031593. Accessed October 16, 2021.

  8. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–22.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372:509–18.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Solomon MM, Lama JR, Glidden DV, et al. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS. 2014;28:851–9.

    Article  CAS  PubMed  Google Scholar 

  11. Mugwanya KK, Wyatt C, Celum C, et al. Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial. JAMA Intern Med. 2015;175:246–54.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kasonde M, Niska RW, Rose C, et al. Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana. PLoS One. 2014;9:e90111.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mulligan K, Glidden DV, Anderson PL, et al. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized,double-blind,placebo-controlled trial. Clin Infect Dis. 2015;61:572–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lehman DA, Baeten JM, McCoy CO, et al. Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. J Infect Dis. 2015;211:1211–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Gibas KM, van den Berg P, Powell VE, Krakower DS. Drug resistance during HIV pre-exposure prophylaxis. Drugs. 2019 Apr;79(6):609–619.

  16. Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008;359:1429–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/ AdultandAdolescentGL.pdf. Accessed October 3,2021.

  18. Brelot A, Chakrabarti LA. CCR5 revisited: How mechanisms of HIV entry govern AIDS pathogenesis. J Mol Biol. 2018 Aug 17;430(17):2557–2589.

  19. Gulick RM, Wilkin TJ, Chen YQ, et al. Phase 2 study of the safety and tolerability of maraviroc-containing regimens to prevent HIV infection in men who have sex with men (MSM) (HPTN 069/ACTG A5305)”. J Infect Dis. 2017 Jan 15;215(2):238–246.

  20. Haberer JE, Bangsberg DR, Baeten JM, et al. Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm. AIDS. 2015 Jul;17(11):1277–85. 29(.

    Article  Google Scholar 

  21. Hendrix CW, Chen BA, Guddera V, et al. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLoS ONE. 2013;8(1):e55013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Emory JF, Seserko LA, Marzinke MA. Development and bioanalytical validation of a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist maraviroc in human plasma. Clin Chim Acta. 2014 Apr 20;431:198–205.

  23. Hendrix CW, Andrade A, Bumpus NN, et al. Dose frequency ranging pharmacokinetic study of tenofovir-emtricitabine after directly observed dosing in healthy volunteers to establish adherence benchmarks (HPTN 066). AIDS Res Hum Retroviruses. 2016 Jan;32(1):32–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yelland LN, Salter AB, Ryan P. Performance of the modified poisson regression approach for estimating relative risks from clustered prospective data. Am J Epidemiol. 2011 Oct;15(8):984–92. 174(.

    Article  Google Scholar 

  25. Landovitz RJ, Donnell D, Clement ME, et al. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021 Aug;12(7):595–608. 385(.

    Article  Google Scholar 

  26. Gulick RM, Fatkenheuer G, Burnside R, et al. Five-year safety evaluation of maraviroc in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr. 2014;65:78–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Taiwo BO, Chan ES, Fichtenbaum CJ, et al. Less bone loss with maraviroc- vs tenofovir-containing antiretroviral therapy in the AIDS clinical trials group A5303 study. Clin Infect Dis. 2015;61:1179–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gulick RM, Wilkin TJ, Chen YQ, et al. Phase 2 safety and tolerability study of maraviroc-containing regimens to prevent HIV infection in women (HPTN 069/ACTG A5305): a randomized trial. Ann Intern Med. 2017;167:384–93.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Massud I, Aung W, Martin A, et al. Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues. J Virol. 2013;87:8952–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Coll J, Molto J, Boix J, et al. Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers. AIDS. 2015;29:2149–54.

    Article  CAS  PubMed  Google Scholar 

  31. Fleishaker DL, Garcia Meijide JA, et al. Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial. Arthritis Res Ther. 2012;14:R11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cohen SE, Vittinghoff E, Bacon O, et al. High interest in preexposure prophylaxis among men who have sex with men at risk for HIV infection: baseline data from the US PrEP demonstration project. J Acquir Immune Defic Syndr. 2015;68(4):439–48.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Amico KR, Stirratt MJ. Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of evidence. Clin Infect Dis. 2014;59(Suppl 1):55–60.

    Article  Google Scholar 

  34. Liu AY, Cohen SE, Vittinghoff E, et al. Preexposure prophylaxis for HIV infection integrated with municipal- and community-based sexual health services. JAMA Intern Med. 2016;176(1):75–84.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Volk JE, Marcus JL, Phengrasamy T, et al. No new HIV infections with increasing use of HIV preexposure prophylaxis in a clinical practice setting. Clin Infect Dis. 2015;61(10):1601–3.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hoenigl M, Morgan E, Franklin D, et al. Self-initiated continuation of and adherence to HIV pre-exposure prophylaxis (PrEP) after PrEP demonstration project roll-off in men who have sex with men: associations with risky decision making, impulsivity/disinhibition, and sensation seeking. J Neurovirol. 2019 Jun;25(3):324–30.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Finlayson T, Cha S, Xia M, et al. Changes in HIV preexposure prophylaxis awareness and use among men who have sex with men—20 urban areas, 2014 and 2017. MMWR. 2019;68:597–603.

    PubMed  PubMed Central  Google Scholar 

  38. Kanny D, Jeffries WL, Chapin-Bardales J, et al. Racial/ethnic disparities in HIV preexposure prophylaxis among men who have sex with men—23 urban areas, 2017. MMWR. 2019;68:801–6.

    PubMed  PubMed Central  Google Scholar 

  39. Wu H, Mendoza MC, Huang YA, Hayes T, Smith DK, Hoover KW. Uptake of HIV preexposure prophylaxis among commercially insured persons-United States, 2010–2014. Clin Infect Dis. 2017 Jan 15;64(2):144–149.

  40. Amico KR. Adherence to preexposure chemoprophylaxis: the behavioral bridge from efficacy to effectiveness. Curr Opin HIVAIDS. 2012;7:542–8.

    Article  Google Scholar 

  41. Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020 Jul;25(10246):239–54. 396(.

    Article  Google Scholar 

  42. Mayer KH, Safren SA, Elsesser SA, et al. “Optimizing Pre-Exposure Antiretroviral Prophylaxis Adherence in Men Who Have Sex with Men: Results of a Pilot Randomized Controlled Trial of “Life-Steps for PrEP”. AIDS Behav. 2017 May;21(5):1350–60.

    Article  PubMed  PubMed Central  Google Scholar 

  43. AVAC Global Advocacy for HIV Prevention. PrEP. Available at: www.avac.org/PrEP. Accessed March 16,2022.

Download references

Funding

The study was funded by the AIDS Program of the National Institute of Allergy and Infectious Diseases, which supports the HIV Prevention Trials Network (HPTN) and the AIDS Clinical Trials Group (ACTG).

Author information

Authors and Affiliations

  1. The Fenway Institute, Fenway Health, Harvard Medical School, Harvard University, 1340 Boylston St, 02215, Boston, MA, United States

    Kenneth H. Mayer MD

  2. Statistical Center for HIV/AIDS Research (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA, United States

    Krista Yuhas & Ying Q. Chen

  3. University of Michigan School of Public Health, Ann Arbor, MI, United States

    K. Rivet Amico

  4. Weill Cornell Medicine, New York, NY, United States

    Timothy Wilkin & Roy M. Gulick

  5. UCLA Center for Clinical AIDS Research & Education, Los Angeles, CA, United States

    Raphael J. Landovitz

  6. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States

    Paul Richardson, Mark A. Marzinke, Craig . W Hendrix & Susan H. Eshleman

  7. Seagen, Bothell, WA, United States

    Leslie M. Cottle

  8. Clinical Prevention Research Branch, Prevention Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States

    Wairimu Chege

  9. HIV Clinical Trials Unit, University of North Carolina, Chapel Hill, NC, United States

    Cheryl Marcus

  10. Global HIV Prevention Strategy, ViiV Healthcare – Research Triangle Park, Research Triangle Park, NC, United States

    Alex R. Rinehart

  11. Medical Affairs, Gilead Sciences, 12. FHI 360, Foster City, Durham, CA, NC, United States

    James F. Rooney

  12. FHI 360, Durham, NC, United States

    Philip Andrew & Marybeth McCauley

  13. Department of Medicine, Case Western Reserve University, Cleveland, OH, United States

    Robert A. Salata

  14. Milken Institute School of Public Health, George Washington University, Washington, DC, United States

    Manya Magnus

  15. Johns Hopkins University School of Medicine, Baltimore, MD, United States

    Jason E. Farley

  16. San Francisco Department of Public Health, Bridge HIV, San Francisco, CA, United States

    Albert Y. Liu

  17. Hospital of the University of Pennsylvania, Philadelphia, PA, United States

    Ian Frank

  18. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States

    Ken Ho

  19. University of Puerto Rico, San Juan, Puerto Rico

    Jorge Santana

  20. University of Washington School of Medicine, Seattle, WA, United States

    Joanne D. Stekler

Authors
  1. Kenneth H. Mayer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Krista Yuhas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Rivet Amico
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Timothy Wilkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raphael J. Landovitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mark A. Marzinke
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Craig . W Hendrix
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Susan H. Eshleman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Leslie M. Cottle
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cheryl Marcus
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wairimu Chege
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Alex R. Rinehart
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. James F. Rooney
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Philip Andrew
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Robert A. Salata
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Manya Magnus
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jason E. Farley
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Albert Y. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ian Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Ken Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Jorge Santana
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Joanne D. Stekler
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Ying Q. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Marybeth McCauley
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Roy M. Gulick
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

HPTN 069/ACTG 5305 Study Team

Contributions

KHM was protocol co-chair, developed the analysis plan for this paper in conjunction with YQ and KY, and wrote the final draft; RG and TW were the other protocol chairs, who oversaw the conduct of the trial, and contributed to the development of the manuscript; KRA was the primary behavioral scientist for the protocol, who contributed to the analysis of the behavioral aspects of the trial; MM, PA, and LC oversaw the conduct of the trial, and coordinated site activities, and ensured data quality (LC); MM and CH oversaw the pharmacologic analyses in the trial, and ARR, JFR coordinated the provision of study medication and assisted in the analyses of the pharmacological aspects of the trial; RL, CM, WC, RS, MM, JEF, AYL, IF, KH, JS, JDS oversaw site activities involved in participant recruitment and subsequent activities in the trial, and provided input in the interpretation of the data and drafting of this manuscript.

Corresponding author

Correspondence to Kenneth H. Mayer MD.

Ethics declarations

Conflicts of interest/competing interests

Dr. Mayer has received research grant funding from Gilead Sciences and Merck, Inc, and has served on scientific advisory boards for Gilead Sciences, Merck, and ViiV.

Ethics approval

The protocol was approved by the Institutional Review Boards of all of the participating sites.

Consent to participate

All participants were educated about the protocol by study staff who were trained by the HPTN for the conduct of the trial, and then reviewed an IRB approved informed consent document. If they felt that their questions were addressed and wanted to participate in the study, they then were asked to sign the document.

Consent for publication

Study protocol prohibited the sharing of individual data. Participants agreed to allow for sharing of de-identified data with the Statistical Data Management Center of the HPTN, at the Fred Hutchinson Cancer Center.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mayer, K.H., Yuhas, K., Amico, K.R. et al. Sexual behavior and medication adherence in men who have sex with men participating in a pre-exposure prophylaxis study of combinations of Maraviroc, Tenofovir Disoproxil Fumarate and/or Emtricitabine (HPTN 069/ACTG 5305). AIDS Behav 26, 4107–4114 (2022). https://doi.org/10.1007/s10461-022-03736-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10461-022-03736-z

Keywords

  • PrEP
  • Tenofovir
  • Maraviroc
  • MSM
  • HIV prevention