Skip to main content

Advertisement

SpringerLink
Log in

Point-of-care and Near Real-time Testing for Antiretroviral Adherence Monitoring to HIV Treatment and Prevention

  • The Science of Prevention (JD Stekler and JM Baeten, Section Editors)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In this report, we review the need for point-of-care (POC) or near real-time testing for antiretrovirals, progress in the field, evidence for guiding implementation of these tests globally, and future directions in objective antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) adherence monitoring.

Recent Findings

Two cornerstones to end the HIV/AIDS pandemic are ART, which provides individual clinical benefits and eliminates forward transmission, and PrEP, which prevents HIV acquisition with high effectiveness. Maximizing the individual and public health benefits of these powerful biomedical tools requires high and sustained antiretroviral adherence. Routine monitoring of medication adherence in individuals receiving ART and PrEP may be an important component in interpreting outcomes and supporting optimal adherence. Existing practices and subjective metrics for adherence monitoring are often inaccurate or unreliable and, therefore, are generally ineffective for improving adherence. Laboratory measures of antiretroviral concentrations using liquid chromatography tandem mass spectrometry have been utilized in research settings to assess medication adherence, although these are too costly and resource-intensive for routine use.

Summary

Newer, less costly technologies such as antibody-based methods can provide objective drug-level measurement and may allow for POC or near-patient adherence monitoring in clinical settings. When coupled with timely and targeted counseling, POC drug-level measures can support adherence clinic-based interventions to ART or PrEP in near real time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Joint United Nations Programme on HIV/AIDS (UNAIDS). Global Report 2019: Report on the global AIDS epidemic. Geneva; 2019.

  2. Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutieŕrez F, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807–18.

    PubMed  CAS  Google Scholar 

  3. Joint United Nations Programme on HIV/AIDS (UNAIDS). Understanding Fast-Track Targets: Accelerating Action to End the AIDS Epidemic by 2030. 2015 Available from: https://www.unaids.org/sites/default/files/media_asset/201506_JC2743_Understanding_FastTrack_en.pdf

  4. US Department of Health and Human Services (DHHS). What is ‘Ending the HIV Epidemic: A Plan for America’? [Internet]. HIV.gov. [cited 2019 Nov 7]. Available from: https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview

  5. Joint United Nations Programme on HIV/AIDS (UNAIDS). 90-90-90 An ambitious treatment target to help end the AIDS epidemic [Internet]. Geneva; 2014. Available from: http://unaids.org/sites/default/files/media_asset/90-90-90_en.pdf

  6. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med. 2016;375(9):830–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  7. Brault MA, Spiegelman D, Hargreaves J, Nash D, Vermund SH. Treatment as prevention: concepts and challenges for reducing HIV incidence. J Acquir Immune Defic Syndr. 2019;82:S104–12.

    PubMed  PubMed Central  Google Scholar 

  8. Molina JM, Charreau I, Chidiac C, Pialoux G, Cua E, Delaugerre C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018;18(3):308–17.

    PubMed  CAS  Google Scholar 

  9. 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.

    PubMed  PubMed Central  CAS  Google Scholar 

  10. 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.

    PubMed  PubMed Central  CAS  Google Scholar 

  11. Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, 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.

    PubMed  Google Scholar 

  12. World Health Organization (WHO). Policy brief: WHO expands recommendation on oral pre-exposure prophylaxis of HIV infection (PrEP) [Internet]. Geneva; 2015. Available from: http://apps.who.int/iris/bitstream/handle/10665/197906/WHO_HIV_2015.48_eng.pdf;jsessionid=FD090759CBB747974F6F77E7F020202D?sequence=1

  13. Smith DK, Handel V, Wolitski M, Richard J, Stryker JE, Hall HI, et al. Vital signs: estimated percentages and numbers of adults with indications for preexposure prophylaxis to prevent HIV acquisition — United States, 2015. Morb Mortal Wkly Rep. 2015;64(46):1291–5.

    Google Scholar 

  14. Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;12(4):151.

    Google Scholar 

  15. Arnsten JH, Demas PA, Farzadegan H, Grant RW, Gourevitch MN, Chang C-J, et al. Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring. Clin Infect Dis. 2001;33(8):1417–23.

    PubMed  PubMed Central  CAS  Google Scholar 

  16. Haberer JE, Musinguzi N, Boum Y, Siedner MJ, Mocello AR, Hunt PW, et al. Duration of antiretroviral therapy adherence interruption is associated with risk of virologic rebound as determined by real-time adherence monitoring in rural Uganda. J Acquir Immune Defic Syndr. 2015;70(4):386–92.

    PubMed  PubMed Central  CAS  Google Scholar 

  17. Bell KM, Haberer JE. Actionable adherence monitoring: technological methods to monitor and support adherence to antiretroviral therapy. Curr HIV/AIDS Rep. 2018;15(5):388–96.

    PubMed  PubMed Central  Google Scholar 

  18. Chaiyachati KH, Ogbuoji O, Price M, Suthar AB, Negussie EK, Bärnighausen T. Interventions to improve adherence to antiretroviral therapy: a rapid systematic review. AIDS. 2014;28(Suppl 2).

  19. Fox MP, Rosen S. Retention of adult patients on antiretroviral therapy in low- and middle-income countries: systematic review and meta-analysis 2008-2013. J Acquir Immune Defic Syndr. 2015;69(1):98–108.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. 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 

  21. Pearson CR, Simoni JM, Hoff P, Kurth AE, Martin DP. Assessing antiretroviral adherence via electronic drug monitoring and self-report: an examination of key methodological issues. AIDS Behav. 2007;11(2):161–73.

    PubMed  PubMed Central  Google Scholar 

  22. Simoni JM, Kurth AE, Pearson CR, Pantalone DW, Merrill JO, Frick PA. Self-report measures of antiretroviral therapy adherence: a review with recommendations for HIV research and clinical management. AIDS Behav. 2006;10(3):227–45.

    PubMed  PubMed Central  Google Scholar 

  23. 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 

  24. Orrell C, Cohen K, Leisegang R, Bangsberg DR, Wood R, Maartens G. Comparison of six methods to estimate adherence in an ART-naïve cohort in a resource-poor setting: which best predicts virological and resistance outcomes? AIDS Res Ther. 2017;14(1):20.

    PubMed  PubMed Central  Google Scholar 

  25. Walshe L, Saple DG, Mehta SH, Shah B, Bollinger RC, Gupta A. Physician estimate of antiretroviral adherence in India: poor correlation with patient self-report and viral load. AIDS Patient Care STDs. 2010;24(3):189–95.

    PubMed  PubMed Central  Google Scholar 

  26. Haberer JE, Robbins GK, Ybarra M, Monk A, Ragland K, Weiser SD, et al. Real-time electronic adherence monitoring is feasible, comparable to unannounced pill counts, and acceptable. AIDS Behav. 2012;16(2):375–82.

    PubMed  PubMed Central  Google Scholar 

  27. Agot K, Taylor D, Corneli AL, Wang M, Ambia J, Kashuba ADM, et al. Accuracy of self-report and pill-count measures of adherence in the FEM-PrEP clinical trial: implications for future HIV-prevention trials. AIDS Behav. 2015;19(5):743–51.

    PubMed  Google Scholar 

  28. Saberi P, Chakravarty D, Ming K, Legnitto D, Gandhi M, Johnson MO, et al. Moving antiretroviral adherence assessments to the modern era: correlations among three novel measures of adherence. AIDS Behav. 2019;24(1):284–90.

    Google Scholar 

  29. Genn L, Chapman J, Okatch H, Abell N, Marukutira T, Tshume O, et al. Pharmacy refill data are poor predictors of virologic treatment outcomes in adolescents with HIV in Botswana. AIDS Behav. 2019;23(8):2130–7.

    PubMed  PubMed Central  Google Scholar 

  30. Acri T, TenHave TR, Chapman JC, Bogner HR, Gross R. Lack of association between retrospectively collected pharmacy refill data and electronic drug monitoring of antiretroviral adherence. AIDS Behav. 2010;14(4):748–54.

    PubMed  Google Scholar 

  31. Grossberg R, Gross R. Use of pharmacy refill data as a measure of antiretroviral adherence. Curr HIV/AIDS Rep. 2007;4(4):187–91.

    PubMed  Google Scholar 

  32. McMahon JH, Jordan MR, Kelley K, Bertagnolio S, Hong SY, Wanke CA, et al. Pharmacy adherence measures to assess adherence to antiretroviral therapy: review of the literature and implications for treatment monitoring. Clin Infect Dis. 2011;52(4):493–506.

    PubMed  PubMed Central  Google Scholar 

  33. Luma HN, Mbatchou Ngahane BH, Mapoure YN, Mengjo NB, Temfack E, Joko HA, et al. Cross-sectional assessment of three commonly used measures of adherence to combination antiviral therapy in a resource limited setting. Int J STD AIDS. 2015;28(1):69–76.

    Google Scholar 

  34. Kunutsor S, Walley J, Katabira E, Muchuro S, Balidawa H, Namagala E, et al. Clinic attendance for medication refills and medication adherence amongst an antiretroviral treatment cohort in Uganda: a prospective study. AIDS Res Treat. 2010;2010:872396.

    PubMed  PubMed Central  Google Scholar 

  35. Bastard M, Pinoges L, Balkan S, Szumilin E, Ferreyra C, Pujades-Rodriguez M. Timeliness of clinic attendance is a good predictor of virological response and resistance to antiretroviral drugs in HIV-infected patients. PLoS One. 2012;7(11):7.

    Google Scholar 

  36. 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 

  37. World Health Organization (WHO), US President’s Emergency Plan for AIDS Relief (PEPFAR), Joint United Nations Programme on HIV/AIDS (UNAIDS). Task shifting: rational redistribution of tasks among health workforce teams: global recommendations and guidelines. Geneva; 2007.

  38. Grimsrud A, Kaplan R, Bekker L-G, Myer L. Outcomes of a nurse-managed service for stable HIV-positive patients in a large South African public sector antiretroviral therapy programme. Tropical Med Int Health. 2014;19(9):1029–39.

    Google Scholar 

  39. Sanne I, Orrell C, Fox MP, Conradie F, Ive P, Zeinecker J, et al. Nurse versus doctor management of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomised non-inferiority trial. Lancet. 2010;376(9734):33–40.

    PubMed  PubMed Central  Google Scholar 

  40. Sherr K, Pfeiffer J, Mussa A, Vio F, Gimbel S, Micek M, et al. The role of nonphysician clinicians in the rapid expansion of HIV care in Mozambique. J Acquir Immune Defic Syndr. 2009 Nov;52(Suppl 1):S20–3.

    PubMed  PubMed Central  Google Scholar 

  41. Brooks KM, Anderson PL. Pharmacologic-based methods of adherence assessment in HIV prevention. Clin Pharmacol Ther. 2018 Dec 1;104(6):1056–9.

    PubMed  PubMed Central  Google Scholar 

  42. Hendrix CW, Andrade A, Bumpus NN, Kashuba AD, Marzinke MA, Moore A, 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 Jan;32(1):32–43.

    PubMed  CAS  Google Scholar 

  43. Koenig H, Mounzer K, Daughtridge G, Sloan C, Lalley-Chareczko L, Moorthy G, et al. Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre-exposure prophylaxis. HIV Med. 2017 Jul;18(6):412–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  44. Drain PK, Kubiak RW, Siriprakaisil O, Klinbuayaem V, Quame-Amaglo J, Sukrakanchana P-O, et al. Urine Tenofovir concentrations correlate with plasma and relates to TDF adherence: a randomized directly-observed pharmacokinetic trial (TARGET study). Clin Infect Dis. 2019;69(9):1647.

    Google Scholar 

  45. Haaland RE, Martin A, Livermont T, Fountain J, Dinh C, Holder A, et al. Brief report: urine emtricitabine and tenofovir concentrations provide markers of recent antiretroviral drug exposure among HIV-negative men who have sex with men. J Acquir Immune Defic Syndr. 2019 Nov 1;82(3):252–6.

    PubMed  CAS  Google Scholar 

  46. Fonsart J, Saragosti S, Taouk M, Peytavin G, Bushman L, Charreau I, et al. Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial. J Antimicrob Chemother. 2017;72(2):478–85.

    PubMed  CAS  Google Scholar 

  47. Castillo-Mancilla JR, Bushman LR, Meditz A, Seifert SM, Zheng J-H, Guida LA, et al. Emtricitabine-triphosphate in dried blood spots (DBS) as a marker of recent dosing. In: Conference on Retroviruses and Opportunistic Infections. Seattle; 2015.

  48. Seifert SM, Chen X, Meditz AL, Castillo-Mancilla JR, Gardner EM, Predhomme JA, et al. Intracellular tenofovir and emtricitabine anabolites in genital, rectal, and blood compartments from first dose to steady state. AIDS Res Hum Retrovir. 2016 Nov 1;32(10–11):981–91.

    PubMed  CAS  Google Scholar 

  49. 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.

    PubMed  Google Scholar 

  50. Donnell D, Baeten JM, Bumpus NN, Brantley J, Bangsberg DR, Haberer JE, et al. HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):340–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Fonner VA, Dalglish SL, Kennedy CE, Baggaley R, O’Reilly KR, Koechlin FM, et al. Effectiveness and safety of oral HIV preexposure prophylaxis for all populations. AIDS. 2016 Jul 31;30(12):1973–83.

    PubMed  PubMed Central  Google Scholar 

  52. Phillips TK, Sinxadi P, Abrams EJ, Zerbe A, Orrell C, Hu N-C, et al. A comparison of plasma efavirenz and tenofovir, dried blood spot tenofovir-diphosphate, and self-reported adherence to predict virologic suppression among South African women. J Acquir Immune Defic Syndr. 2019 Jul 1;81(3):311–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  53. de Lastours V, Fonsart J, Burlacu R, Gourmel B, Molina J-M. Concentrations of tenofovir and emtricitabine in saliva: implications for preexposure prophylaxis of oral HIV acquisition. Antimicrob Agents Chemother. 2011 Oct;55(10):4905–7.

    PubMed  PubMed Central  Google Scholar 

  54. Krause J, Subklew-Sehume F, Kenyon C, Colebunders R. Acceptability of HIV self-testing: a systematic literature review. BMC Public Health. 2013 Dec 8;13(1):735.

    PubMed  PubMed Central  Google Scholar 

  55. Kowalczyk Mullins TL, Braverman PK, Dorn LD, Kollar LM, Kahn JA. Adolescent preferences for human immunodeficiency virus testing methods and impact of rapid tests on receipt of results. J Adolesc Health. 2010 Feb;46(2):162–8.

    PubMed  Google Scholar 

  56. Manchikanti L, Malla Y, Wargo BW, Cash KA, Pampati V, Damron KS, et al. Protocol for accuracy of point of care (POC) or in-office urine drug testing (immunoassay) in chronic pain patients: a prospective analysis of immunoassay and liquid chromatography tandem mass spectometry (LC/MS/MS). Pain Physician. 2010;13(1).

  57. Yager J, Castillo-Mancilla JR, Ibrahim ME, Brooks KM, McHugh C, MaWhinney S, et al. Tenofovir-diphosphate in dried blood spots following escalating TAF/FTC dosing. In: Conference on Retroviruses and Opportunistic Infections. Seattle; 2019.

  58. Zheng J-H, Rower C, McAllister K, Castillo-Mancilla J, Klein B, Meditz A, et al. Application of an intracellular assay for determination of tenofovir-diphosphate and emtricitabine-triphosphate from erythrocytes using dried blood spots. J Pharm Biomed Anal. 2016 Apr 15;122:16–20.

    PubMed  PubMed Central  CAS  Google Scholar 

  59. Liu AY, Yang Q, Huang Y, Bacchetti P, Anderson PL, Jin C, et al. Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP). PLoS One. 2014 Jan 8;9(1):e83736.

    PubMed  PubMed Central  Google Scholar 

  60. Adams JL, Sykes C, Menezes P, Prince HMA, Patterson KB, Fransen K, et al. Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence? J Acquir Immune Defic Syndr. 2013 Mar 1;62(3):260–6.

    PubMed  PubMed Central  CAS  Google Scholar 

  61. Castillo-Mancilla JR, Zheng J-H, Rower JE, Meditz A, Gardner EM, Predhomme J, et al. Tenofovir, emtricitabine, and tenofovir diphosphate in dried blood spots for determining recent and cumulative drug exposure. AIDS Res Hum Retrovir. 2013 Feb;29(2):384–90.

    PubMed  CAS  Google Scholar 

  62. Anderson PL, Liu AY, Castillo-Mancilla JR, Gardner EM, Seifert SM, McHugh C, et al. Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy. Antimicrob Agents Chemother. 2018;1(1):62.

    Google Scholar 

  63. Kearney BP, Flaherty JF, Shah J. Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin Pharmacokinet. 2004;43(9):595–612.

    PubMed  CAS  Google Scholar 

  64. Koss CA, Bacchetti P, Hillier SL, Livant E, Horng H, Mgodi N, et al. Differences in cumulative exposure and adherence to tenofovir in the VOICE, iPrEx OLE, and PrEP demo studies as determined via hair concentrations. AIDS Res Hum Retrovir. 2017 Aug;33(8):778–83.

    PubMed  CAS  Google Scholar 

  65. 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 

  66. Castillo-Mancilla JR, Morrow M, Coyle RP, Coleman SS, Gardner EM, Zheng J-H, et al. Tenofovir diphosphate in dried blood spots is strongly associated with viral suppression in individuals with human immunodeficiency virus infections. Clin Infect Dis. 2019 Apr 8;68(8):1335–42.

    PubMed  CAS  Google Scholar 

  67. Morrow M, MaWhinney S, Coyle RP, Coleman SS, Gardner EM, Zheng J-H, et al. Predictive value of tenofovir diphosphate in dried blood spots for future viremia in persons living with HIV. J Infect Dis. 2019.

  68. Koren G, Bellaish E, Maman K. Hair analysis for drug-facilitated crime: the critical role of hair growth rate. J Forensic Sci. 2019;64(5):1574–5.

    PubMed  CAS  Google Scholar 

  69. Gandhi M, Glidden DV, Liu A, Anderson PL, Horng H, Defechereux P, et al. Strong correlation between concentrations of tenofovir (TFV) emtricitabine (FTC) in hair and TFV diphosphate and FTC triphosphate in dried blood spots in the iPrEx open label extension: implications for pre-exposure prophylaxis adherence monitoring. J Infect Dis. 2015 Nov 1;212(9):1402–6.

    PubMed  PubMed Central  CAS  Google Scholar 

  70. Gandhi M, Murnane PM, Bacchetti P, Elion R, Kolber MA, Cohen SE, et al. Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen. AIDS. 2017 Oct 23;31(16):2245–51.

    PubMed  PubMed Central  CAS  Google Scholar 

  71. Thaden JT, Gandhi M, Okochi H, Hurt CB, McKellar MS. Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination. AIDS. 2018;32(9):F1–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  72. Gilliland WM, Prince HMA, Poliseno A, Kashuba ADM, Rosen EP. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging of human hair to characterize longitudinal profiles of the antiretroviral maraviroc for adherence monitoring. Anal Chem. 2019;91(16):10816–22.

    PubMed  PubMed Central  CAS  Google Scholar 

  73. Cohen SE, Sachdev D, Lee SA, Scheer S, Bacon O, Chen MJ, et al. Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report. Lancet HIV. 2019;6(1):e43–50.

    Google Scholar 

  74. Gandhi M, Ameli N, Bacchetti P, Anastos K, Gange SJ, Minkoff H, et al. Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. Clin Infect Dis. 2011 May;52(10):1267–75.

    PubMed  PubMed Central  CAS  Google Scholar 

  75. Tüdos AJ, Besselink GAJ, Schasfoort RBM. Trends in miniaturized total analysis systems for point-of-care testing in clinical chemistry. Lab Chip. 2001 Dec 1;1(2):83–95.

    PubMed  Google Scholar 

  76. Pratt GW, Fan A, Melakeberhan B, Klapperich CM. A competitive lateral flow assay for the detection of tenofovir. Anal Chim Acta. 2018 Aug 9;1017:34–40.

    PubMed  PubMed Central  CAS  Google Scholar 

  77. Gandhi M, Bacchetti P, Rodrigues WC, Spinelli M, Koss CA, Drain PK, et al. Development and validation of an immunoassay for tenofovir in urine as a real-time metric of antiretroviral adherence. EClinicalMedicine. 2018;34(2):255–60.

    Google Scholar 

  78. Gandhi M, Wang G, King R, Rodrigues WC, Vincent M, Glidden DV, et al. Development and validation of the first point-of-care assay to objectively monitor adherence to HIV treatment and prevention in real-time in routine settings. AIDS. 2019;34(2):255–60.

    Google Scholar 

  79. Daughtridge G, Hebel S, Larabee L, Patani H, Cohen A, Fischl M, et al. Development and clinical use case of a urine tenofovir adherence test. In: HIV Diagnostics Conference. Atlanta; 2019.

  80. Gandhi M, Bacchetti P, Spinelli MA, Okochi H, Baeten JM, Siriprakaisil O, et al. Brief report: validation of a urine tenofovir immunoassay for adherence monitoring to PrEP and ART and establishing the cutoff for a point-of-care test. J Acquir Immune Defic Syndr. 2019 May 1;81(1):72–7.

    PubMed  PubMed Central  Google Scholar 

  81. US Centers for Disease Control and Prevention (CDC). Screening in clinical settings | Screening for HIV [Internet]. 2019 [cited 2019 Dec 1]. Available from: https://www.cdc.gov/hiv/clinicians/screening/clinical-settings.html

  82. World Health Organization (WHO). Consolidated guidelines on HIV testing services 2015 [Internet]. 2015 [cited 2019 Dec 1]. Available from: http://apps.who.int/iris/bitstream/10665/179870/1/9789241508926_eng.pdf?ua=1&ua=1

  83. World Health Organization (WHO). WHO recommends HIV self-testing: Policy brief [Internet]. World Health Organization (WHO). Geneva: World Health Organization; 2016 [cited 2019 Jul 23]. Available from: https://www.who.int/hiv/pub/vct/who-recommends-hiv-self-testing/en/

  84. ClinicalTrials.gov. Identifier NCT04341779, Simplifying treatment and monitoring for HIV. Bethesda: National Library of Medicine (US); 2020.

  85. Bardon AR, Simoni JM, Layman LM, Stekler JD, Drain PK. Utility and acceptability of a point-of-care urine tenofovir test for adherence to HIV pre-exposure prophylaxis and antiretroviral therapy: a qualitative assessment among U.S. clients and providers. 2019;Manuscript.

  86. Wu G, Zaman MH. Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings. Bull World Health Organ. 2012 Dec;90(12):914–20.

    PubMed  PubMed Central  Google Scholar 

  87. Johnson CC, Kennedy C, Fonner V, Siegfried N, Figueroa C, Dalal S, et al. Examining the effects of HIV self-testing compared to standard HIV testing services: a systematic review and meta-analysis. J Int AIDS Soc. 2017;20(1).

  88. Vojnov L, Markby J, Boeke C, Harris L, Ford N, Peter T. POC CD4 testing improves linkage to HIV care and timeliness of ART initiation in a public health approach: a systematic review and meta-analysis. Roques P, editor. PLoS One. 2016 May 13;11(5):e0155256.

  89. Rice B, Boulle A, Schwarcz S, Shroufi A, Rutherford G, Hargreaves J. The continuing value of CD4 cell count monitoring for differential HIV care and surveillance. J Med Internet Res. 2019;1(3):21.

    Google Scholar 

  90. World Health Organization (WHO). Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy [Internet]. Geneva; 2017 [cited 2020 Jan 12]. Available from: https://www.who.int/hiv/pub/guidelines/advanced-HIV-disease/en/

  91. Drain PK, Dorward J, Bender A, Lillis L, Marinucci F, Sacks J, et al. Point-of-care HIV viral load testing: an essential tool for a sustainable global HIV/AIDS response. Clin Microbiol Rev. 2019;19:32(3).

    Google Scholar 

  92. Agutu CA, Ngetsa CJ, Price MA, Rinke de Wit TF, Omosa-Manyonyi G, Sanders EJ, et al. Systematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and care. PLoS One. 2019;14(6).

  93. Drain PK, Dorward J, Violette LR, Quame-Amaglo J, Thomas KK, Samsunder N, et al. Point-of-care HIV viral load testing combined with task shifting to improve treatment outcomes: an open-label non-inferiority randomized controlled trial to Simplify HIV TREAtment and Monitoring (STREAM Study). Lancet HIV. 2020;In Press.

  94. Nicholas S, Poulet E, Wolters L, Wapling J, Rakesh A, Amoros I, et al. Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi. J Int AIDS Soc. 2019;22(8).

  95. Estill J, Egger M, Blaser N, Vizcaya LS, Garone D, Wood R, et al. Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study. AIDS. 2013 Jun 1;27(9):1483–92.

    PubMed  Google Scholar 

  96. de Necker M, de Beer JC, Stander MP, Connell CD, Mwai D. Economic and public health impact of decentralized HIV viral load testing: a modelling study in Kenya. PLoS One. 2019;1(2):14.

    Google Scholar 

  97. Simeon K, Sharma M, Dorward J, Naidoo J, Dlamini N, Moodley P, et al. Comparative cost analysis of point-of-care versus laboratory-based testing to initiate and monitor HIV treatment in South Africa. PLoS One. 2019;14(10).

  98. Koester KA, Liu A, Eden C, Amico KR, McMahan V, Goicochea P, et al. Acceptability of drug detection monitoring among participants in an open-label pre-exposure prophylaxis study. AIDS Care. 2015 Oct 3;27(10):1199–204.

    PubMed  PubMed Central  Google Scholar 

  99. Montgomery ET, Mensch B, Musara P, Hartmann M, Woeber K, Etima J, 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.

    PubMed  PubMed Central  Google Scholar 

  100. Landovitz RJ, Beymer M, Kofron R, Amico KR, Psaros C, Bushman L, et al. Plasma tenofovir levels to support adherence to TDF/FTC preexposure prophylaxis for HIV prevention in MSM in Los Angeles, California. J Acquir Immune Defic Syndr [Internet]. 2017 [cited 2019 May 17];76(5):501–11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28902074.

  101. Celum C, Mgodi N, Bekker L-G, Hosek S, Donnell D, Anderson PL, et al. PrEP adherence and effect of drug level feedback among young African women in HPTN 082. In: International AIDS Society. Mexico City; 2019.

  102. ClinicalTrials.gov. Identifier NCT03935464, Point-of-care Urine Monitoring of Adherence (PUMA): testing a real-time urine assay of tenofovir in PrEP (PUMA) [Internet]. Bethesda: National Library of Medicine (US); 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT03935464

  103. ClinicalTrials.gov. Identifer NCT04038060, The PrEP (Pre-exposure Prophylaxis) SMART study [Internet]. Bethesda: National Library of Medicine (US); 2019. Available from: https://clinicaltrials.gov/ct2/show/study/NCT04038060

  104. Spreen WR, Margolis DA, Pottage JC. Long-acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013;8(6):565–71.

    PubMed  PubMed Central  CAS  Google Scholar 

  105. Devereaux ZJ, Reynolds CA, Fischer JL, Foley CD, DeLeeuw JL, Wager-Miller J, et al. Matrix-assisted ionization on a portable mass spectrometer: analysis directly from biological and synthetic materials. Anal Chem. 2016;88(22):10831–6.

    PubMed  CAS  Google Scholar 

  106. Da Silva LC, Pereira I, De Carvalho TC, Allochio Filho JF, Romão W, Vaz BG. Paper spray ionization and portable mass spectrometers: a review. Anal Methods. 2019;11(8):999–1013.

    Google Scholar 

  107. Li L, Chen TC, Ren Y, Hendricks PI, Cooks RG, Ouyang Z. Mini 12, miniature mass spectrometer for clinical and other applications - Introduction and characterization. Anal Chem. 2014;86(6):2909–16.

    PubMed  PubMed Central  CAS  Google Scholar 

  108. Gao L, Sugiarto A, Harper JD, Cooks RG, Ouyang Z. Design and characterization of a multisource hand-held tandem mass spectrometer. Anal Chem. 2008 Oct 1;80(19):7198–205.

    PubMed  CAS  Google Scholar 

  109. Jannetto PJ, Fitzgerald RL. Effective use of mass spectrometry in the clinical laboratory. Clin Chem. 2016 Jan 1;62(1):92–8.

    PubMed  CAS  Google Scholar 

  110. Patel TS, Kaakeh R, Nagel JL, Newton DW, Stevenson JG. Cost analysis of implementing matrix- assisted laser desorption ionization-time of flight mass spectrometry plus real-time antimicrobial stewardship intervention for bloodstream infections. J Clin Microbiol. 2017;55(1):60–7.

    PubMed  Google Scholar 

  111. Heaney LM, Jones DJ, Suzuki T. Mass spectrometry in medicine: a technology for the future? Futur Sci OA. 2017;3(3).

  112. Pu F, Pandey S, Bushman LR, Anderson PL, Ouyang Z, Cooks RG. Direct quantitation of tenofovir diphosphate in human blood with mass spectrometry for adherence monitoring. Anal Bioanal Chem. 2020;

  113. Ataullakhanov FI, Vitvitsky VM. What determines the intracellular ATP concentration. Biosci Rep. 2002;22(5–6):501–11.

    PubMed  CAS  Google Scholar 

  114. Seok Y, Jang H, Oh J, Joung HA, Kim MG. A handheld lateral flow strip for rapid DNA extraction from staphylococcus aureus cell spiked in various samples. Biomed Phys Eng Express. 2019 Apr;17:5(3).

    Google Scholar 

  115. VanDine RW, Mahesh Babu U, Sambursky RP. US8614101B2 - in situ lysis of cells in lateral flow immunoassays [Internet]. US; 2009 [cited 2019 Dec 10]. Available from: https://patents.google.com/patent/US8614101B2/en

  116. Castillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng JH, et al. Emtricitabine-triphosphate in dried blood spots as a marker of recent dosing. Antimicrob Agents Chemother. 2016 Nov 1;60(11):6692–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  117. Olanrewaju AO, Posner JD. An enzymatic assay to measure long-term adherence to pre-exposure prophylaxis and antiretroviral therapy. bioRxiv Bioeng.

  118. Olanrewaju A, Sullivan B, Bender A, Zhang J, Lo T, Bardon A, et al. Development of an enzymatic assay for quantitative measurement of adherence to antiretroviral therapy and pre-exposure prophylaxis. In: The 14th International Conference on HIV Treatment and Prevention Adherence. Miami; 2019.

  119. Ruane PJ, DeJesus E, Berger D, Markowitz M, Bredeek UF, Callebaut C, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013;63(4):449–55.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Global Health, Schools of Medicine and Public Health, University of Washington, 325 Ninth Ave, UW Box 359927, Seattle, WA, 98104-2420, USA

    Paul K. Drain, Ashley R. Bardon, Jane M. Simoni & Connie Celum

  2. Department of Medicine, School of Medicine, University of Washington, 325 Ninth Ave, UW Box 359927, Seattle, WA, 98104-2420, USA

    Paul K. Drain & Connie Celum

  3. Department of Epidemiology, School of Public Health, University of Washington, 325 Ninth Ave, UW Box 359927, Seattle, WA, 98104-2420, USA

    Paul K. Drain & Ashley R. Bardon

  4. Department of Psychology, University of Washington, Seattle, USA

    Jane M. Simoni

  5. Department of Gender, Women, and Sexuality Studies, University of Washington, Seattle, USA

    Jane M. Simoni

  6. PHPT/IRD 174, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    Tim R. Cressey

  7. Harvard T.H. Chan School of Public Health, Harvard University, Boston, USA

    Tim R. Cressey

  8. Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK

    Tim R. Cressey

  9. Department of Pharmaceutical Sciences, University of Colorado, Aurora, Aurora, CO, USA

    Pete Anderson

  10. Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Derin Sevenler

  11. Department of Mechanical Engineering, University of Washington, Seattle, USA

    Ayokunle O. Olanrewaju

  12. Department of Medicine, University of California, San Francisco, San Francisco, USA

    Monica Gandhi

Authors
  1. Paul K. Drain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashley R. Bardon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jane M. Simoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tim R. Cressey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pete Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Derin Sevenler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ayokunle O. Olanrewaju
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Monica Gandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Connie Celum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul K. Drain.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any data from studies with human or animal subjects that was performed by any of the authors and has not already been published elsewhere.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on The Science of Prevention

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Drain, P.K., Bardon, A.R., Simoni, J.M. et al. Point-of-care and Near Real-time Testing for Antiretroviral Adherence Monitoring to HIV Treatment and Prevention. Curr HIV/AIDS Rep 17, 487–498 (2020). https://doi.org/10.1007/s11904-020-00512-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-020-00512-3

Keywords

Search

Navigation