Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project

Abstract

Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12 months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled; 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood samples had plasma drug concentrations indicative of taking 7 pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15–1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12 months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555.

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References

  1. 1.

    WHO. Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations—2016 update. Lyon: World Health Organisation; 2016.

    Google Scholar 

  2. 2.

    Holt M, Lea T, Schmidt HM, et al. Willingness to use and have sex with men taking HIV pre-exposure prophylaxis (PrEP): results of online surveys of Australian gay and bisexual men, 2011–2015. Sex Transm Infect. 2017;93(6):438–44.

    Article  PubMed  Google Scholar 

  3. 3.

    Mera RMS, Palmer B, Mayer G, et al. Truvada (TVD) for HIV pre-exposure prophylaxis (PrEP) utilization in the United States (2013–2015). AIDS 2016; Durban [Abstract 10159].

  4. 4.

    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(27):2587–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

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

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381(9883):2083–90.

    Article  PubMed  Google Scholar 

  7. 7.

    Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373(23):2237–46.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Corneli AL, Deese J, Wang M, et al. FEM-PrEP: adherence patterns and factors associated with adherence to a daily oral study product for pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2014;66(3):324–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    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.

    Article  PubMed  Google Scholar 

  11. 11.

    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):20642.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Amico KR, Mehrotra M, Avelino-Silva VI, et al. Self-reported recent PrEP dosing and drug detection in an open label PrEP study. AIDS Behav. 2016;20(7):1535–40.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Martin M, Vanichseni S, Suntharasamai P, et al. Factors associated with the uptake of and adherence to HIV pre-exposure prophylaxis in people who have injected drugs: an observational, open-label extension of the Bangkok Tenofovir Study. Lancet HIV. 2017;4(2):e59–66.

    Article  PubMed  Google Scholar 

  14. 14.

    McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387(10013):53–60.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    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 

  16. 16.

    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 

  17. 17.

    Hoagland B, Moreira RI, De Boni RB, et al. High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV infection: the PrEP Brasil demonstration project. J Int AIDS Soc. 2017;20(1):1–14.

    Article  Google Scholar 

  18. 18.

    Fonner VA, Dalglish SL, Kennedy CE, et al. Effectiveness and safety of oral HIV preexposure prophylaxis for all populations. AIDS. 2016;30(12):1973–83.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    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 Retrovir. 2016;32(1):32–43.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–97.

    Article  CAS  Google Scholar 

  21. 21.

    Conn VS, Ruppar TM, Enriquez M, Cooper P. Medication adherence interventions that target subjects with adherence problems: systematic review and meta-analysis. Res Soc Adm Pharm. 2016;12(2):218–46.

    Article  Google Scholar 

  22. 22.

    Baxi SM, Liu A, Bacchetti P, et al. Comparing the novel method of assessing PrEP adherence/exposure using hair samples to other pharmacologic and traditional measures. J Acquir Immune Defic Syndr. 2015;68(1):13–20.

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Amico KR, Marcus JL, McMahan V, et al. Study product adherence measurement in the iPrEx placebo-controlled trial: concordance with drug detection. J Acquir Immune Defic Syndr. 2014;66(5):530–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Dai JY, Hendrix CW, Richardson BA, et al. Pharmacological measures of treatment adherence and risk of HIV infection in the VOICE study. J Infect Dis. 2016;213(3):335–42.

    Article  PubMed  Google Scholar 

  25. 25.

    UNAIDS. Prevention gap report. Geneva: Joint United Nations Programme on HIV/AIDS; 2016.

    Google Scholar 

  26. 26.

    Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia: annual surveillance report 2017. Sydney: Kirby Institute; 2017.

    Google Scholar 

  27. 27.

    Vaccher S, Grulich A, McAllister J, et al. Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW demonstration project PRELUDE. BMJ Open. 2016;6(6):e012179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    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 

  29. 29.

    Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4(151):151ra25.

    Article  CAS  Google Scholar 

  30. 30.

    Stirratt MJ, Dunbar-Jacob J, Crane HM, et al. Self-report measures of medication adherence behavior: recommendations on optimal use. Transl Behav Med. 2015;5(4):470–82.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Zablotska IB, Selvey C, Guy R, et al. Expanded HIV pre-exposure prophylaxis (PrEP) implementation in communities in New South Wales, Australia (EPIC-NSW): design of an open label, single arm implementation trial. BMC Public Health. 2018;18(1):297.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Zablotska I, Vaccher S, Bloch M, et al. High adherence to HIV pre-exposure prophylaxis and no HIV seroconversions despite high levels of risk behaviour and STIs: the Australian demonstration study PrELUDE. AIDS Behav. 2018. https://doi.org/10.1007/s10461-018-2290-3.

    Article  Google Scholar 

  33. 33.

    Vaccher SJ, Grulich AE, Haire BG, et al. Validation of participant eligibility for pre-exposure prophylaxis: baseline data from the PRELUDE demonstration project. PLoS ONE. 2017;12(9):e0185398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Mayer KH, Oldenburg CE, Novak DS, Elsesser SA, Krakower DS, Mimiaga MJ. Early adopters: correlates of HIV chemoprophylaxis use in recent online samples of US men who have sex with men. AIDS Behav. 2016;20(7):1489–98.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Prestage G, Grierson J, Bradley J, Hurley M, Hudson J. The role of drugs during group sex among gay men in Australia. Sex Health. 2009;6(4):310–7.

    Article  PubMed  Google Scholar 

  36. 36.

    Hirshfield S, Schrimshaw EW, Stall RD, Margolis AD, Downing MJ Jr, Chiasson MA. Drug use, sexual risk, and syndemic production among men who have sex with men who engage in group sexual encounters. Am J Public Health. 2015;105(9):1849–58.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Dis. 2014;14(9):820–9.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Blumenthal J, Jain S, Dube M, et al. Recent HIV risk behavior and partnership type predict PrEP adherence in men who have sex with men. ID Week; San Diego; 2017 [Abstract 882].

  39. 39.

    Liu A, Glidden DV, Anderson PL, et al. Patterns and correlates of PrEP drug detection among MSM and transgender women in the Global iPrEx Study. J Acquir Immune Defic Syndr. 2014;67(5):528–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Haberer JE, Baeten JM, Campbell J, et al. Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa. PLoS Med. 2013;10(9):e1001511.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Martin M, Vanichseni S, Suntharasamai P, et al. The impact of adherence to preexposure prophylaxis on the risk of HIV infection among people who inject drugs. AIDS. 2015;29(7):819–24.

    Article  PubMed  Google Scholar 

  42. 42.

    Gandhi M, Glidden DV, Liu A, et al. Concentrations of TFV-DP/FTC-TP in dried blood spots and TFV/FTC in hair are strongly correlated in iPrEx OLE: implications for PrEP adherence monitoring. J Infect Dis. 2015;212:1402–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Podsadecki TJ, Vrijens BC, Tousset EP, Rode RA, Hanna GJ. “White coat compliance” limits the reliability of therapeutic drug monitoring in HIV-1-infected patients. HIV Clin Trials. 2008;9(4):238–46.

    Article  PubMed  Google Scholar 

  44. 44.

    Marcus JL, Hurley LB, Hare CB, et al. Preexposure prophylaxis for HIV prevention in a large integrated health care system: adherence, renal safety, and discontinuation. J Acquir Immune Defic Syndr. 2016;73(5):540–6.

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    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(4):572–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Mannheimer S, Loquere A, Franks J, et al. HPTN 067/ADAPT study: a comparison of daily and intermittent pre-exposure prophylaxis (PrEP) dosing for HIV prevention in men who have sex with men and transgender women in New York City. IAS; Vancouver; 2015 [Abstract MOAC0305LB].

  47. 47.

    Anderson PL, Garcia-Lerma JG, Heneine W. Nondaily preexposure prophylaxis for HIV prevention. Curr Opin HIV AIDS. 2016;11(1):94–101.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Elsesser SA, Oldenburg CE, Biello KB, et al. Seasons of risk: anticipated behavior on vacation and interest in episodic antiretroviral pre-exposure prophylaxis (PrEP) among a large national sample of U.S. men who have sex with men (MSM). AIDS Behav. 2016;20(7):1400–7.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Namey E, Agot K, Ahmed K, et al. When and why women might suspend PrEP use according to perceived seasons of risk: implications for PrEP-specific risk-reduction counselling. Cult Health Sex. 2016;18(9):1081–91.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Lal L, Audsley J, Murphy DA, et al. Medication adherence, condom use and sexually transmitted infections in Australian preexposure prophylaxis users. AIDS. 2017;31(12):1709–14.

    Article  PubMed  Google Scholar 

  51. 51.

    WHO. WHO implementation tool for pre-exposure prophylaxis (PrEP) of HIV infection. Module 1: clinical. Geneva: World Health Organisation; 2017.

    Google Scholar 

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Acknowledgements

PRELUDE Study Team Author Contributors Mark Bloch, Andrew Carr, Ching (Yvonne) Cheung (study clinical coordinator), Rosalind Foster, Christopher Gianacas (clinical data manager), Andrew Grulich, Rebecca Guy, Martin Holt, John Kaldor, Brent Mackie, Kenneth Mayer, John McAllister, Anna McNulty, Dean Murphy, Catriona Ooi, Cathy Pell, Isobel M. Poynten, Garrett Prestage, Nathan Ryder, David Templeton, Stefanie Vaccher (behavioural data manager), John de Wit, Edwina Wright, and Iryna Zablotska (chief investigator and protocol chair). NSW HIV Prevention Partnership Project Team Author Contributors Denton Callander, David Cooper, Craig Cooper, Levinia Crooks, Tim Duck, Andrew Grulich (principal investigator and protocol co-chair), Rebecca Guy, Jo Holden, Martin Holt, John Kaldor, Phillip Keen, Anthony Kelleher, Jo Mitchell, Garrett Prestage, Karen Price, Christine Selvey (principal investigator and protocol co-chair), Heather-Marie Schmidt, Barbara Telfer, Bill Whittaker, David Wilson, John de Wit and Iryna Zablotska. Participating clinics Clinic 16 at Royal North Shore Hospital, Holdsworth House Medical Practice, Newcastle Sexual Health Service, RPA Sexual Health, St Vincent’s Hospital HIV Immunology and Infectious Diseases Unit, Sydney Sexual Health Centre, Taylor Square Private Clinic, and Western Sydney Sexual Health Centre. Laboratories and clinical supplies Johns Hopkins Clinical Pharmacology Analytical Laboratory (CPAL, Baltimore, USA), St Vincent’s Centre for Applied Medical Research (AMR, Sydney, Australia), SydPath (Sydney, Australia). Community partner organisations ACON (AIDS Council of NSW) and Positive Life NSW.

Funding

This analysis was supported by funding from an NHMRC Partnership Project grant (Grant #1092852), the NSW Ministry of Health, and UNSW Sydney. An in-kind supply of study medication was provided by Gilead Sciences. The Kirby Institute receives funding from the Australian Government Department of Health and is affiliated with the Faculty of Medicine, UNSW Sydney.

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Correspondence to Stefanie J. Vaccher.

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Conflicts of interest

AEG has research funding from Seqirus, Gilead, Viiv, and in-kind research support from Hologic. He has received travel funding from Gilead. IBZ has received research funding and in-kind support (supply of the study medication) from Gilead Sciences Inc. Authors SJV, MAM, BGH, DJT, NR, AM, and RF declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Vaccher, S.J., Marzinke, M.A., Templeton, D.J. et al. Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project. AIDS Behav 23, 1287–1296 (2019). https://doi.org/10.1007/s10461-018-2353-5

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Keywords

  • Pre-exposure prophylaxis (PrEP)
  • Adherence
  • HIV
  • Facilitated recall
  • Blood tenofovir concentrations