Smartphone-Based Contingency Management Intervention to Improve Pre-Exposure Prophylaxis Adherence: Pilot Trial

John T Mitchell, Sara LeGrand, Lisa B Hightow-Weidman, Mehri S McKellar, Angela Dm Kashuba, Mackenzie Cottrell, Tony McLaurin, Goutam Satapathy, F Joseph McClernon, John T Mitchell, Sara LeGrand, Lisa B Hightow-Weidman, Mehri S McKellar, Angela Dm Kashuba, Mackenzie Cottrell, Tony McLaurin, Goutam Satapathy, F Joseph McClernon

Abstract

Background: Pre-exposure prophylaxis (PrEP) provides a strong preventative benefit to individuals at risk for HIV. While PrEP adherence is highly correlated with its efficacy, adherence rates are variable both across and within persons.

Objective: The objective of this study was to develop and pilot-test a smartphone-based intervention, known as mSMART, that targets PrEP adherence. mSMART provides contingency management in the form of monetary incentives for daily PrEP adherence based on a real-time adherence assessment using a camera-based medication event-monitoring tool as well as medication reminders, PrEP education, individualized behavioral strategies to address PrEP adherence barriers, and medication adherence feedback.

Methods: This was a 4-week open-label, phase I trial in a community sample of young men who have sex with men already on PrEP (N=10).

Results: Although adherence composite scores corresponding to PrEP biomarkers indicated that 90% (9/10) of the sample already had an acceptable baseline adherence in the protective range, by the end of the 4-week period, the scores improved for 30% (3/10) of the sample-adherence did not worsen for any participants. Participants reported mean PrEP adherence rates of 91% via daily entries in mSMART. At the end of the 4-week period, participants indicated acceptable ratings of satisfaction, usability, and willingness to recommend mSMART to others. There were no technical difficulties associated with smartphone compatibility, user misunderstandings about mSMART features that interfered with daily use, or study attrition.

Conclusions: This study is the first to apply contingency management to PrEP adherence. Findings indicated that mSMART is feasible and acceptable. Such an adherence intervention administered via a user-friendly smartphone app can allow for widespread dissemination. Future efficacy trials are needed.

Trial registration: ClinicalTrials.gov NCT02895893; https://ichgcp.net/clinical-trials-registry/NCT02895893 (Accessed by Webcite at http://www.webcitation.org/72JskjDJq).

Keywords: HIV; mobile health; preexposure prophylaxis.

Conflict of interest statement

Conflicts of Interest: JTM and FJM have served as site principal investigator and coinvestigator on a subcontract from Intelligent Automation Incorporated (IAI) funded by the National Institutes of Health (N44DA132236) to develop mSMART for a different indication (ie, smoking cessation). JTM also served as site principal investigator on a subcontract from Intelligent Automation Incorporated funded under N43DA130022. GS is employed by IAI and represents IAI as mSMART product owner.

©John T Mitchell, Sara LeGrand, Lisa B Hightow-Weidman, Mehri S. McKellar, Angela DM Kashuba, Mackenzie Cottrell, Tony McLaurin, Goutam Satapathy, F Joseph McClernon. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 10.09.2018.

Figures

Figure 1
Figure 1
Sample recruitment and participation flowchart. TFV: tenofovir, TFV-DP: tenofovir-diphosphate.
Figure 2
Figure 2
mSMART home screen.
Figure 3
Figure 3
Percentage of time the individual participants logged a dose in mSMART using either the camera-based medication event-monitoring tool or manual entry option.
Figure 4
Figure 4
Percentage of time the camera-based medication event-monitoring tool was used among participants when they logged a dose in mSMART.

References

    1. Grant R, Anderson P, McMahan V, Liu A, Amico K, Mehrotra M. Results of the iPrEx open-label extension (iPrEx OLE) in men and transgender women who have sex with men: PrEP uptake, sexual practices, and HIV incidence. International AIDS Conference; 2014; Melbourne, Australia.
    1. Molina J, Capitant C, Charreau I, Meyer L, Spire B, Pialoux G. On demand PrEP with oral TDF-FTC in MSM: results of the ANRS Ipergay Trial. Conference on Retroviruses Opportunistic Infections; 2015; Seattle, WA.
    1. Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, Hosek S, Mosquera C, Casapia M, Montoya O, Buchbinder S, Veloso VG, Mayer K, Chariyalertsak S, Bekker L, Kallas EG, Schechter M, Guanira J, Bushman L, Burns DN, Rooney JF, Glidden DV, iPrEx ST. 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 Sep;14(9):820–9. doi: 10.1016/S1473-3099(14)70847-3.
    1. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapía M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernández T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker L, Mayer KH, Kallás EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng J, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV, iPrEx ST. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587–99. doi: 10.1056/NEJMoa1011205.
    1. Baeten J, Heffron R, Kidoguchi L, Celum C. Near elimination of HIV transmission in a demonstration project of PrEP and ART. Conference on Retroviruses Opportunistic Infections; 2015; Seattle, WA.
    1. Martin M, Mock PA, Curlin ME, Vanichseni S. Preliminary follow-up of injecting drug users receiving preexposure prophylaxis. Conference on Retroviruses Opportunistic Infections; 2015; Seattle, WA.
    1. Peterson L, Taylor D, Roddy R, Belai G, Phillips P, Nanda K, Grant R, Clarke EEK, Doh AS, Ridzon R, Jaffe HS, Cates W. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials. 2007 May 25;2(5):e27. doi: 10.1371/journal.pctr.0020027.
    1. McCormack S, Dunn D. Pragmatic open-label randomised trial of preexposure prophylaxis: the PROUD Study. Conference on Retroviruses Opportunistic Infections; 2015; Seattle, WA.
    1. Grohskopf LA, Chillag KL, Gvetadze R, Liu AY, Thompson M, Mayer KH, Collins BM, Pathak SR, Oʼhara B, Ackers ML, Rose CE, Grant RM, Paxton LA, Buchbinder SP. Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):79–86. doi: 10.1097/QAI.0b013e31828ece33.
    1. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C, Partners PST. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399–410. doi: 10.1056/NEJMoa1108524.
    1. Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, Chiamwongpaet S, Kitisin P, Natrujirote P, Kittimunkong S, Chuachoowong R, Gvetadze RJ, McNicholl JM, Paxton LA, Curlin ME, Hendrix CW, Vanichseni S, Bangkok TSG. 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 Jun 15;381(9883):2083–90. doi: 10.1016/S0140-6736(13)61127-7.
    1. Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, Palanee T, Nakabiito C, van DSA, Noguchi L, Hendrix CW, Dai JY, Ganesh S, Mkhize B, Taljaard M, Parikh UM, Piper J, Mâsse B, Grossman C, Rooney J, Schwartz JL, Watts H, Marzinke MA, Hillier SL, McGowan IM, Chirenje ZM. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015 Feb 5;372(6):509–18. doi: 10.1056/NEJMoa1402269.
    1. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, Henderson FL, Pathak SR, Soud FA, Chillag KL, Mutanhaurwa R, Chirwa LI, Kasonde M, Abebe D, Buliva E, Gvetadze RJ, Johnson S, Sukalac T, Thomas VT, Hart C, Johnson JA, Malotte CK, Hendrix CW, Brooks JT, TDF2 SG. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012 Aug 2;367(5):423–34. doi: 10.1056/NEJMoa1110711.
    1. Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, Malahleha M, Owino F, Manongi R, Onyango J, Temu L, Monedi MC, Mak'Oketch P, Makanda M, Reblin I, Makatu SE, Saylor L, Kiernan H, Kirkendale S, Wong C, Grant R, Kashuba A, Nanda K, Mandala J, Fransen K, Deese J, Crucitti T, Mastro TD, Taylor D, FEM-Pr EG. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012 Aug 2;367(5):411–22. doi: 10.1056/NEJMoa1202614.
    1. Corneli AL, Deese J, Wang M, Taylor D, Ahmed K, Agot K, Lombaard J, Manongi R, Kapiga S, Kashuba A, Van DL, FEM-Pr EG. 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 Jul 1;66(3):324–31. doi: 10.1097/QAI.0000000000000158.
    1. Amico KR, Stirratt MJ. Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of evidence. Clin Infect Dis. 2014 Jul;59 Suppl 1:S55–60. doi: 10.1093/cid/ciu266.
    1. Centers for Disease Control and Prevention . Archived at: . 2015. Trends in U.S. HIV diagnoses, 2005-2014 .
    1. Koss CA, Hosek SG, Bacchetti P, Anderson PL, Liu AY, Horng H, Benet LZ, Kuncze K, Louie A, Saberi P, Wilson CM, Gandhi M. Comparison of measures of adherence to HIV preexposure prophylaxis among adolescent and young men who have sex with men in the United States. Clin Infect Dis. 2018 Jan 06;66(2):213–219. doi: 10.1093/cid/cix755.
    1. Hosek SG, Landovitz RJ, Kapogiannis B, Siberry GK, Rudy B, Rutledge B, Liu N, Harris DR, Mulligan K, Zimet G, Mayer KH, Anderson P, Kiser JJ, Lally M, Brothers J, Bojan K, Rooney J, Wilson CM. Safety and feasibility of antiretroviral preexposure prophylaxis for adolescent men who have sex with men Aged 15 to 17 years in the United States. JAMA Pediatr. 2017 Nov 01;171(11):1063–1071. doi: 10.1001/jamapediatrics.2017.2007.
    1. Mayer KH, Safren SA, Elsesser SA, Psaros C, Tinsley JP, Marzinke M, Clarke W, Hendrix C, Wade TS, Haberer J, Mimiaga MJ. 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):1350–1360. doi: 10.1007/s10461-016-1606-4.
    1. Miller G. The smartphone psychology manifesto. Perspect Psychol Sci. 2012 May;7(3):221–37. doi: 10.1177/1745691612441215. doi: 10.1177/1745691612441215.
    1. Pew Research Center. 2017. [2018-03-23]. Mobile Fact Sheet
    1. Klasnja P, Pratt W. Healthcare in the pocket: mapping the space of mobile-phone health interventions. J Biomed Inform. 2012 Feb;45(1):184–98. doi: 10.1016/j.jbi.2011.08.017.
    1. Ahmed I, Ahmad NS, Ali S, Ali S, George A, Saleem DH, Uppal E, Soo J, Mobasheri MH, King D, Cox B, Darzi A. Medication adherence apps: review and content analysis. JMIR Mhealth Uhealth. 2018 Mar 16;6(3):e62. doi: 10.2196/mhealth.6432.
    1. Moore DJ, Jain S, Dubé MP, Daar ES, Sun X, Young J, Corado K, Ellorin E, Milam J, Collins D, Blumenthal J, Best BM, Anderson P, Haubrich R, Morris SR. Randomized controlled trial of daily text messages to support adherence to PrEP in at-risk for HIV individuals: the TAPIR Study. Clin Infect Dis. 2017 Nov 24; doi: 10.1093/cid/cix1055.
    1. Sullivan PS, Driggers R, Stekler JD, Siegler A, Goldenberg T, McDougal SJ, Caucutt J, Jones J, Stephenson R. Usability and acceptability of a mobile comprehensive HIV prevention app for men who have sex with men: a pilot study. JMIR Mhealth Uhealth. 2017 Mar 09;5(3):e26. doi: 10.2196/mhealth.7199.
    1. Available from: . Archived at: . P3 (Prepared, Protected, emPowered) (P3) .
    1. Petry NM, Rash CJ, Byrne S, Ashraf S, White WB. Financial reinforcers for improving medication adherence: findings from a meta-analysis. Am J Med. 2012 Sep;125(9):888–96. doi: 10.1016/j.amjmed.2012.01.003.
    1. Mbuagbaw L, Sivaramalingam B, Navarro T, Hobson N, Keepanasseril A, Wilczynski NJ, Haynes RB, Patient Adherence Review (PAR) Team Interventions for enhancing adherence to antiretroviral therapy (ART): a systematic review of high quality studies. AIDS Patient Care STDS. 2015 May;29(5):248–66. doi: 10.1089/apc.2014.0308.
    1. Landovitz RJ, Fletcher JB, Shoptaw S, Reback CJ. Contingency management facilitates the use of postexposure prophylaxis among stimulant-using men who have sex with men. Open Forum Infect Dis. 2015 Jan;2(1):ofu114. doi: 10.1093/ofid/ofu114.
    1. Menza TW, Hughes JP, Celum CL, Golden MR. Prediction of HIV acquisition among men who have sex with men. Sex Transm Dis. 2009 Sep;36(9):547–55. doi: 10.1097/OLQ.0b013e3181a9cc41.
    1. United States Public Health Service. 2014. Preexposure prophylaxis for the prevention of HIV infection in the United States: clinical practice guideline .
    1. United States Public Health Service Preexposure prophylaxis for the prevention of HIV infection in the United States: clinical providers supplement. 2014 .
    1. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606–13.
    1. Skinner HA. The drug abuse screening test. Addict Behav. 1982;7(4):363–71.
    1. Saunders JB, Aasland OG, Babor TF, de LFJR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II. Addiction. 1993 Jun;88(6):791–804.
    1. Hahn SR, Park J, Skinner EP, Yu-Isenberg KS, Weaver MB, Crawford B, Flowers PW. Development of the ASK-20 adherence barrier survey. Curr Med Res Opin. 2008 Jul;24(7):2127–38. doi: 10.1185/03007990802174769.
    1. Intelligent Automation, Inc. [2018-03-23]. mSMART Medication Aide
    1. Mitchell JT, McIntyre EM, English JS, Dennis MF, Beckham JC, Kollins SH. A pilot trial of mindfulness meditation training for ADHD in adulthood: impact on core symptoms, executive functioning, and emotion dysregulation. J Atten Disord. 2017 Nov;21(13):1105–1120. doi: 10.1177/1087054713513328.
    1. Brooke J. SUS-A quick and dirty usability scale. Usability Eval Ind. 1996;189:4–7.
    1. Vilardaga R, Rizo J, Kientz JA, McDonell MG, Ries RK, Sobel K. User Experience evaluation of a smoking cessation app in people with serious mental illness. Nicotine Tob Res. 2016 May;18(5):1032–8. doi: 10.1093/ntr/ntv256.
    1. Adams JL, Sykes C, Menezes P, Prince HMA, Patterson KB, Fransen K, Crucitti T, De BI, Van DL, Kashuba ADM. 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. doi: 10.1097/QAI.0b013e3182794723.
    1. Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, McMahan V, Bushman LR, Casapía M, Montoya-Herrera O, Veloso VG, Mayer KH, Chariyalertsak S, Schechter M, Bekker L, Kallás EG, Grant RM, iPrEx ST. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012 Sep 12;4(151):151ra125. doi: 10.1126/scitranslmed.3004006.
    1. Nanda N, Satapathy G, Holt L, McClernon FJ, Mitchell JT. mSMART: personalized mobile app for improving medication adherence. 3rd annual mHealth@Duke conference; 2015; Durham, NC.
    1. Amico KR, Mansoor LE, Corneli A, Torjesen K, van der Straten A. Adherence support approaches in biomedical HIV prevention trials: experiences, insights and future directions from four multisite prevention trials. AIDS Behav. 2013 Jul;17(6):2143–55. doi: 10.1007/s10461-013-0429-9.
    1. Gilmore HJ, Liu A, Koester KA, Amico KR, McMahan V, Goicochea P, Vargas L, Lubensky D, Buchbinder S, Grant R. Participant experiences and facilitators and barriers to pill use among men who have sex with men in the iPrEx pre-exposure prophylaxis trial in San Francisco. AIDS Patient Care STDS. 2013 Oct;27(10):560–6. doi: 10.1089/apc.2013.0116.
    1. Haberer JE, Bangsberg DR, Baeten JM, Curran K, Koechlin F, Amico KR, Anderson P, Mugo N, Venter F, Goicochea P, Caceres C, O'Reilly K. Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm. AIDS. 2015 Jul 17;29(11):1277–85. doi: 10.1097/QAD.0000000000000647.
    1. Liu AY, Cohen SE, Vittinghoff E, Anderson PL, Doblecki-Lewis S, Bacon O, Chege W, Postle BS, Matheson T, Amico KR, Liegler T, Rawlings MK, Trainor N, Blue RW, Estrada Y, Coleman ME, Cardenas G, Feaster DJ, Grant R, Philip SS, Elion R, Buchbinder S, Kolber MA. Preexposure prophylaxis for HIV infection integrated with municipal- and community-based sexual health services. JAMA Intern Med. 2016 Jan;176(1):75–84. doi: 10.1001/jamainternmed.2015.4683.
    1. Fisher J, Fisher W. Peterson JL, DiClemente RJ. editors. Handbook of HIV prevention. 1st ed. New York: Kluwer Academic/Plenum Press; 2000. Theoretical approaches to indivdual-level change in HIV risk behavior.
    1. Aliabadi N, Carballo-Dieguez A, Bakken S, Rojas M, Brown W, Carry M, Mosley JP, Gelaude D, Schnall R. Using the information-motivation-behavioral skills model to guide the development of an HIV prevention smartphone application for high-risk MSM. AIDS Educ Prev. 2015 Dec;27(6):522–37. doi: 10.1521/aeap.2015.27.6.522.
    1. Sauro J. A practical guide to the system usability scale: background, benchmarks,best practices. Measuring Usability LLC. 2011
    1. Mitchell JT, Sweitzer MM, Tunno AM, Kollins SH, McClernon FJ. “I use weed for my ADHD”: a qualitative analysis of online forum discussions on cannabis and ADHD. PLoS One. 2016;11(5):e0156614. doi: 10.1371/journal.pone.0156614.
    1. Mitchell JT, Weisner TS, Jensen PS, Murray DW, Molina BSG, Arnold EL, Hechtman L, Swanson JM, Hinshaw SP, Victor EC, Kollins SH, Wells KC, Belendiuk KA, Blonde A, Nguyen C, Ambriz L, Nguyen JL. How substance users with ADHD perceive the relationship between substance use and emotional functioning. J Atten Disord. 2017 Feb 01;:1087054716685842. doi: 10.1177/1087054716685842.
    1. Mayer KH, Chan PA, Flash CA, Krakower DS. Evolving models and ongoing challenges for HIV pre-exposure prophylaxis implementation in the United States. J Acquir Immune Defic Syndr. 2018 Feb 01;77(2):119–127. doi: 10.1097/QAI.0000000000001579.
    1. Kelley CF, Kahle E, Siegler A, Sanchez T, Del RC, Sullivan PS, Rosenberg ES. Applying a PrEP continuum of care for men who have sex with men in Atlanta, Georgia. Clin Infect Dis. 2015 Nov 15;61(10):1590–7. doi: 10.1093/cid/civ664.
    1. Abaasa A, Hendrix C, Gandhi M, Anderson P, Kamali A, Kibengo F, Sanders EJ, Mutua G, Bumpus NN, Priddy F, Haberer JE. Utility of different adherence measures for PrEP: patterns and incremental value. AIDS Behav. 2018 Apr;22(4):1165–1173. doi: 10.1007/s10461-017-1951-y.
    1. Baker Z, Javanbakht M, Mierzwa S, Pavel C, Lally M, Zimet G, Gorbach P. Predictors of over-reporting HIV pre-exposure prophylaxis (PrEP) adherence among young men who have sex with men (YMSM) in self-reported versus biomarker data. AIDS Behav. 2017 Oct 27; doi: 10.1007/s10461-017-1958-4.
    1. Koss CA, Hosek SG, Bacchetti P, Anderson PL, Liu AY, Horng H, Benet LZ, Kuncze K, Louie A, Saberi P, Wilson CM, Gandhi M. Comparison of measures of adherence to human immunodeficiency virus preexposure prophylaxis among adolescent and young men who have sex with men in the United States. Clin Infect Dis. 2018 Jan 06;66(2):213–219. doi: 10.1093/cid/cix755.
    1. Albert W, Tullis T. Measuring the user experience: collecting, analyzing, and presenting usability metrics. 2nd ed. Amsterdam, Netherlands: Morgan Kaufmann; 2013.
    1. Tullis T, Stetson J. A comparison of questionnaires for assessing website usability. Usability Professionals' Association Conference; 2004; Minneapolis, MN.
    1. Petry NM, Martin B. Low-cost contingency management for treating cocaine- and opioid-abusing methadone patients. J Consult Clin Psychol. 2002 Apr;70(2):398–405.
    1. Petry NM, Martin B, Cooney JL, Kranzler HR. Give them prizes, and they will come: contingency management for treatment of alcohol dependence. J Consult Clin Psychol. 2000 Apr;68(2):250–7.
    1. Petry NM, Martin B, Simcic F. Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic. J Consult Clin Psychol. 2005 Apr;73(2):354–9. doi: 10.1037/0022-006X.73.2.354.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever