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Design and Delivery of Real-Time Adherence Data to Men Who Have Sex with Men Using Antiretroviral Pre-exposure Prophylaxis via an Ingestible Electronic Sensor

Abstract

Once daily tenofovir/emtricitabine when used for pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition but requires consistent medication adherence. The use of ingestible technologies to monitor PrEP adherence can assist in understanding the impact of behavioral interventions. Digital pill systems (DPS) utilize an ingestible radiofrequency emitter integrated onto a gelatin capsule, which permits direct, real-time measurement of medication adherence. DPS monitoring may lead to discovery of nascent episodes of PrEP nonadherence and allow delivery of interventions that prevent the onset of sustained nonadherence. Yet, the acceptance and potential use of DPS in high-risk men who have sex with men (MSM; i.e., those who engage in condomless sex and use substances) is unknown. In this investigation, we conducted individual, semi-structured qualitative interviews with 30 MSM with self-reported non-alcohol substance use to understand their responses to the DPS, willingness and perceived barriers to its use, and their perceptions of its potential utility. We also sought to describe how MSM would potentially interact with a messaging system integrated into the DPS. We identified major themes around improved confidence of PrEP adherence patterns, safety of ingestible radiofrequency sensors, and design optimization of the DPS. They also expressed willingness to interact with messaging contingent on DPS recorded ingestion patterns. These data demonstrate that MSM who use substances find the DPS to be an acceptable method to measure and record PrEP adherence.

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References

  1. Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, et al. Emtricitabine-tenofovir exposure and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4(151):151ra125-151ra125.

    Google Scholar 

  2. Doblecki-Lewis S, Cohen S, Liu A. Clinical treatment options infectious diseases: update on PrEP implementation, adherence, and advances in delivery. Curr Treat Options Infect Dis. 2015;7(2):101–12.

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6):509–18.

    PubMed  PubMed Central  Google Scholar 

  6. Mayer KH, Safren S, Haberer J, Elsesser S, Clarke W, Hendrix CW, et al. Project PrEPARE: high levels of medication adherence with continued condomless sex in U.S. men who have sex with men in an oral PrEP adherence trial. AIDS Res Hum Retroviruses. 2014;30(S1):A23–4.

    Google Scholar 

  7. Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367(5):411–22.

    PubMed  PubMed Central  Google Scholar 

  8. Haberer JE. Current concepts for PrEP adherence in the PrEP revolution: from clinical trials to routine practice. Curr Opin HIV AIDS. 2016;11(1):10–7.

    PubMed  PubMed Central  Google Scholar 

  9. Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, 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.

    PubMed  PubMed Central  Google Scholar 

  10. Liu AY, Cohen SE, Vittinghoff E, Anderson PL, Doblecki-Lewis S, Bacon O, et al. Preexposure prophylaxis for HIV infection integrated with municipal- and community-based sexual health services. JAMA Intern Med. 2016;176(1):75.

    PubMed  PubMed Central  Google Scholar 

  11. Spinelli M, Haberer J, Chai P, Castillo-Mancilla J, Anderson P, Gandhi M. Approaches to objectively measure antiretroviral medication adherence and drive adherence interventions. Curr HIV/AIDS Rep. 2020. https://doi.org/10.1007/s11904-020-00502-5In press.

    Article  PubMed  Google Scholar 

  12. Castillo-Mancilla JR, Haberer JE. Adherence measurements in HIV: new advancements in pharmacologic methods and real-time monitoring. Curr HIV/AIDS Rep. 2018;15(1):49–59.

    PubMed  PubMed Central  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  14. Chai PR, Castillo-Mancilla J, Buffkin E, Darling C, Rosen RK, Horvath KJ, et al. Utilizing an ingestible biosensor to assess real-time medication adherence. J Med Toxicol. 2015;11(4):439–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. El Alili M, Vrijens B, Demonceau J, Evers SM, Hiligsmann M. A scoping review of studies comparing the medication event monitoring system (MEMS) with alternative methods for measuring medication adherence. Br J Clin Pharmacol. 2016;82(1):268–79.

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  17. Garrison LE, Haberer JE. Technological methods to measure adherence to antiretroviral therapy and preexposure prophylaxis. Curr Opin HIV AIDS. 2017;12(5):467–74.

    PubMed  Google Scholar 

  18. Haberer JE, Bangsberg DR, Baeten JM, Curran K, Koechlin F, Amico KR, et al. Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm. AIDS. 2015;29(11):1277–85.

    PubMed  PubMed Central  Google Scholar 

  19. Chai P, Rosen R, Boyer E. Ingestible biosensors for real-time medical adherence monitoring: MyTMed. Proceedings of the annual Hawaii international conference on system science. 2016;3416–23.

  20. Vallejos X, Wu C. Digital medicine: innovative drug-device combination as new measure of medication adherence. J Pharm Technol. 2017;33(4):137–9.

    PubMed Central  Google Scholar 

  21. Hill LM, Golin CE, Pack A, Carda-Auten J, Wallace DD, Cherkur S, et al. Using real-time adherence feedback to enhance communication about adherence to antiretroviral therapy: patient and clinician perspectives. J Assoc Nurses AIDS Care. 2020;31(1):25–34.

    PubMed  PubMed Central  Google Scholar 

  22. Daar ES, Rosen MI, Wang Y, Siqueiros L, Shen J, Guerrero M, et al. Real-time and wireless assessment of adherence to antiretroviral therapy with co-encapsulated ingestion sensor in HIV-infected patients: a pilot study. Clin Transl Sci. 2020;13(1):189–94.

    CAS  PubMed  Google Scholar 

  23. Chai PR, Carreiro S, Innes BJ, Rosen RK, O’Cleirigh C, Mayer KH, et al. Digital pills to measure opioid ingestion patterns in emergency department patients with acute fracture pain: a pilot study. J Med Internet Res. 2017;19(1):e19.

    PubMed  PubMed Central  Google Scholar 

  24. Chai PR, Carreiro S, Innes BJ, Chapman B, Schreiber KL, Edwards RR, et al. Oxycodone ingestion patterns in acute fracture pain with digital pills. Anesth Analg. 2017;125(6):2105–12.

    PubMed  PubMed Central  Google Scholar 

  25. Carreiro S, Smelson D, Ranney M, Horvath KJ, Picard RW, Boudreaux ED, et al. Real-time mobile detection of drug use with wearable biosensors: a pilot study. J Med Toxicol. 2015;11(1):73–9.

    CAS  PubMed  Google Scholar 

  26. Liu H, Daar E, Wang Y, Siqueiros L, Campbell K, Shen J, et al. Pharmacokinetics of coencapsulated antiretrovirals with ingestible sensors. AIDS Res Hum Retroviruses. 2020;36(1):65–74.

    CAS  PubMed  Google Scholar 

  27. Chai PR, Pereira LM, Jambaulikar GD, Carrico AW, O’Cleirigh C, Mayer KH, et al. Short communication: bioequivalence of tenofovir component of tenofovir/rilpivirine/emtricitabine in digital pills. AIDS Res Hum Retroviruses. 2019;35(4):361–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Carey JW, Mejia R, Bingham T, Ciesielski C, Gelaude D, Herbst JH, et al. Drug use, high-risk sex behaviors, and increased risk for recent HIV infection among men who have sex with men in Chicago and Los Angeles. AIDS Behav. 2009;13(6):1084–96.

    PubMed  Google Scholar 

  29. Ostrow DG, Plankey MW, Cox C, Li X, Shoptaw S, Jacobson LP, et al. Specific sex drug combinations contribute to the majority of recent HIV seroconversions among MSM in the MACS. JAIDS J Acquir Immune Defic Syndr. 2009;51(3):349–55.

    PubMed  Google Scholar 

  30. Santos G-M, Coffin PO, Das M, Matheson T, DeMicco E, Raiford JL, et al. Dose-response associations between number and frequency of substance use and high-risk sexual behaviors among HIV-negative substance-using men who have sex with men (SUMSM) in San Francisco. JAIDS J Acquir Immune Defic Syndr. 2013;63(4):540–4.

    PubMed  Google Scholar 

  31. Freeman P. Methamphetamine use and risk for HIV among young men who have sex with men in 8 US cities. Arch Pediatr Adolesc Med. 2011;165(8):736.

    PubMed  PubMed Central  Google Scholar 

  32. Hoenigl M, Chaillon A, Moore DJ, Morris SR, Smith DM, Little SJ. Clear links between starting methamphetamine and increasing sexual risk behavior: a cohort study among men who have sex with men. JAIDS J Acquir Immune Defic Syndr. 2016;71(5):551–7.

    CAS  PubMed  Google Scholar 

  33. Hoenigl M, Chaillon A, Morris SR, Little SJ. HIV infection rates and risk behavior among young men undergoing community-based testing in San Diego. Sci Rep. 2016;6(1):25927.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Vosburgh HW, Mansergh G, Sullivan PS, Purcell DW. A review of the literature on event-level substance use and sexual risk behavior among men who have sex with men. AIDS Behav. 2012;16(6):1394–410.

    PubMed  Google Scholar 

  35. Grov C, Rendina HJ, John SA, Parsons JT. Determining the roles that club drugs, marijuana, and heavy drinking play in PrEP medication adherence among gay and bisexual men: implications for treatment and research. AIDS Behav. 2019;23(5):1277–86.

    PubMed  PubMed Central  Google Scholar 

  36. Hambrick HR, Park SH, Schneider JA, Mayer KH, Carrico AW, Sherman SE, et al. Poppers and PrEP: use of pre-exposure prophylaxis among men who have sex with men who use inhaled nitrites. AIDS Behav. 2018;22(11):3658–72.

    PubMed  PubMed Central  Google Scholar 

  37. Pew Research Center. Internet & Technology Mobile Fact Sheet [Internet]. 2019. https://www.pewresearch.org/internet/fact-sheet/mobile/. Accessed 24 Aug 2020.

  38. Davis FD. Perceived usefulness, perceived ease of use, and user acceptance of information technology. MIS Q. 1989;13(3):319–40.

    Google Scholar 

  39. Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19(6):349–57.

    PubMed  Google Scholar 

  40. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101.

    Google Scholar 

  41. Guest G, MacQueen K, Namey E. Applied thematic analysis. Thousand Oaks: SAGE Publications, Inc.; 2011.

    Google Scholar 

  42. QSR International. NVivo software. 2018.

  43. Ando H, Cousins R, Young C. Achieving saturation in thematic analysis: development and refinement of a codebook. Compr Psychol. 2014;3:03.CP.3.4.

    Google Scholar 

  44. Joint United Nations Programme on HIV/AIDS (UNAIDS). Getting to zero: 2011–2015 strategy [Internet]. Joint United Nations Programme on HIV/AIDS (UNAIDS); 2010. https://www.unaids.org/sites/default/files/sub_landing/files/JC2034_UNAIDS_Strategy_en.pdf.

  45. etectRx®, Inc. etectRx Announces U.S. FDA Clearance of Novel Ingestible Event Marker [Internet]. 2019. https://etectrx.com/etectrx-announces-u-s-fda-clearance-of-novel-ingestible-event-marker/.

  46. Antoni G, Tremblay C, Delaugerre C, Charreau I, Cua E, Rojas Castro D, et al. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post hoc analysis of the ANRS IPERGAY trial. Lancet HIV. 2020;7(2):e113–20.

    PubMed  Google Scholar 

  47. Parienti J-J. On-demand PrEP efficacy: forgiveness or timely dosing. Lancet HIV. 2020;7(2):e79–80.

    PubMed  Google Scholar 

  48. Molina J-M, Charreau I, Spire B, Cotte L, Chas J, Capitant C, et al. Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study. Lancet HIV. 2017;4(9):e402–10.

    PubMed  Google Scholar 

  49. Shrier LA, Koren S, Aneja P, de Moor C. Affect regulation, social context, and sexual intercourse in adolescents. Arch Sex Behav. 2010;39(3):695–705.

    PubMed  Google Scholar 

  50. Smiley SL, Milburn NG, Nyhan K, Taggart T. A systematic review of recent methodological approaches for using ecological momentary assessment to examine outcomes in U.S. based HIV research. Curr HIV/AIDS Rep. 2020;17(4):333–42.

    PubMed  Google Scholar 

  51. Hensel DJ, Fortenberry JD, Harezlak J, Craig D. The feasibility of cell phone based electronic diaries for STI/HIV research. BMC Med Res Methodol. 2012;12(1):75.

    PubMed  PubMed Central  Google Scholar 

  52. Dworkin MS, Panchal P, Wiebel W, Garofalo R, Haberer JE, Jimenez A. A triaged real-time alert intervention to improve antiretroviral therapy adherence among young African American men who have sex with men living with HIV: focus group findings. BMC Public Health. 2019;19(1):394.

    PubMed  PubMed Central  Google Scholar 

  53. Sabin LL, Bachman DeSilva M, Gill CJ, Zhong L, Vian T, Xie W, et al. Improving adherence to antiretroviral therapy with triggered real-time text message reminders: the China adherence through technology study. JAIDS J Acquir Immune Defic Syndr. 2015;69(5):551–9.

    PubMed  Google Scholar 

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Funding

PRC is funded by NIH K23DA044874, R44DA051106 and research funding from Gilead Sciences (ISR-17-1018), Hans and Mavis Psychosocial Foundation and e-ink corporation, KM and CO are funded by NIAID P30AI060354, EWB and RKR are funded by NIH R01DA047236.

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Correspondence to Peter R. Chai.

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This study was funded through unrestricted research funds through the ISR program at Gilead Sciences.

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Chai, P.R., Goodman, G., Bustamante, M. et al. Design and Delivery of Real-Time Adherence Data to Men Who Have Sex with Men Using Antiretroviral Pre-exposure Prophylaxis via an Ingestible Electronic Sensor. AIDS Behav 25, 1661–1674 (2021). https://doi.org/10.1007/s10461-020-03082-y

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Keywords

  • HIV prevention
  • Technology
  • PrEP
  • Digital pill system
  • Ingestible sensors