Improving the Adherence to Antiretroviral Therapy, a Difficult but Essential Task for a Successful HIV Treatment-Clinical Points of View and Practical Considerations

Simona A Iacob, Diana G Iacob, Gheorghita Jugulete, Simona A Iacob, Diana G Iacob, Gheorghita Jugulete

Abstract

HIV infection is responsible for one the most devastating human pandemics. The advent of antiretroviral therapy has changed the course of the pandemic and saved millions of lives. Complex therapeutic regimens have been introduced since 1996 and have contributed to the transformation of HIV infection into a treatable chronic diseases. New types of potent antiretrovirals and their combinations, including "once daily" treatment, have simplified the regimens and diminished side effects. Nevertheless the adherence to antiretroviral therapy remains unsatisfactory and varies between 27 and 80% across different population in various studies, compared with the required level of 95%. The lack of adherence to antiretroviral therapy is a multi-factorial and dynamic process which raises considerable difficulties for long-term follow-up. Current solutions to this problem are complex. These should be applied by a multidisciplinary team and should take into account key features related to both the individual and social factors as well as to the population to whom it belongs (children, teenagers, elderly, marginalized population like drug users, incarcerated patients, sex workers, etc.). Importantly, adherence should continue to be monitored even in patients known to be compliant. In case of subsequent failure the team should identify the reasons for non-adherence and apply the appropriate methods. Where usual methods have no chance of success, a coordinated package of services also known as "harm reduction" can be offered in order to reduce the risks of transmission. The current article analyses the concept of adherence to antiretroviral therapy, the shortcomings of this medication and the methods that can be applied in practice to increase adherence. Emphasis is placed on the analysis of groups at high risk for HIV infection that currently represent the spearhead with which the HIV pandemic is spreading.

Keywords: HIV; adherence; adverse reactions; antiretroviral drugs; antiretroviral treatment; key affected population.

References

    1. ABC Project Team (2018). Ascertaining Barriers for Compliance: Policies for Safe, Effective and Cost-Effective Use of Medicines in Europe Final Report of the ABC Project.
    1. Aharonovich E., Greenstein E., O'Leary A., Johnston B., Seol S. G., Hasin D. S. (2012). HealthCall: technology-based extension of motivational interviewing to reduce non-injection drug use in HIV primary care patients ? a pilot study. AIDS Care 24, 1461–1469. 10.1080/09540121.2012.663882
    1. Altice F. L., Maru DS-Bruce R. D., Springer S. A., Friedland G. H. (2007). Superiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: a prospective, randomized, controlled trial. Clin. Infect. Dis. 45, 770–778. 10.1086/521166
    1. Arage G., Tessema G. A., Kassa H. (2014). Adherence to antiretroviral therapy and its associated factors among children at South Wollo Zone Hospitals, Northeast Ethiopia: a cross-sectional study. BMC Public Health. 14:365. 10.1186/1471-2458-14-365
    1. Arnsten J. H., Demas P. A., Grant R. W., Gourevitch M. N., Farzadegan H., Howard A. A., et al. . (2002). Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. J. Gen. Intern. Med. 17, 377–381. 10.1007/s11606-002-0044-3
    1. Arnsten J., Demas P., Farzadegan H., Grant R., Gourevitch M., Chang C., et al. . (2001). Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring. Clin. Infect. Dis. 33, 1417–1423. 10.1086/323201
    1. Azmeraw D., Wasie B. (2012). Factors associated with adherence to highly active antiretroviral therapy among children in two referral hospitals, northwest Ethiopia. Ethiop. Med. J. 50, 115–124.
    1. Bangsberg D. R., Mundy L. M., Tulsky J. P. (2001). Expanding directly observed therapy: tuberculosis to human immunodeficiency virus. Am. J. Med. 110, 664–666. 10.1016/S0002-9343(01)00729-X
    1. Barai N., Monroe A., Lesko C., Lau B., Hutton H., Yang C., et al. . (2017). The association between changes in alcohol use and changes in antiretroviral therapy adherence and viral suppression among women living with HIV. AIDS Behav. 21, 1836–1845. 10.1007/s10461-016-1580-x
    1. Bartlett J. A. (2002). Addressing the challenges of adherence. J. Acquir. Immune. Defic. Syndr. 29(Suppl. 1), S2–S10. 10.1097/00126334-200202011-00002
    1. Berkman L. F., Syme S. L. (1979). Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda County residents. Am. J. Epidemiol. 109, 186–204. 10.1093/oxfordjournals.aje.a112674
    1. Bhaskaran K., Hamouda O., Sannes M., Boufassa F., Johnson A. M., Lambert P. C., et al. . (2008). Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 300:51. 10.1001/jama.300.1.51
    1. Bierman W. F., van Agtmael M. A., Nijhuis M., Danner S. A., Boucher C. A. (2009). HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review. AIDS 23, 279–291. 10.1097/QAD.0b013e32831c54e5
    1. Cantudo-Cuenca M. R., Jiménez-Galán R., Almeida-González C V., Morillo-Verdugo R. (2014). Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients. J. Manag. Care Pharm. 20, 844–850. 10.18553/jmcp.2014.20.8.844
    1. Carr A., Miller J., Law M., Cooper D. A. (2000). A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 14, F25–F32. 10.1097/00002030-200002180-00001
    1. Centers for Disease Control and Prevention (2014). Understanding the HIV care Continuum. 2014. (cited Oct 14, 2017). Available online at:
    1. Chaiyachati K. H., Ogbuoji O., Price M., Suthar A. B., Negussie E. K., Bärnighausen T. (2014). Interventions to improve adherence to antiretroviral therapy: a rapid systematic review. Wolters Kluwer Heal. 28, 187–204. 10.1097/QAD.0000000000000252
    1. Chesney M. (2003). Adherence to HAART regimens. AIDS Patient Care STDS. 17, 169–177. 10.1089/108729103321619773
    1. Clay P. G., Nag S., Graham C. M., Narayanan S. (2015). Meta-analysis of studies comparing single and multi-tablet fixed dose combination HIV treatment regimens. Medicine 94:e1677. 10.1097/MD.0000000000001677
    1. Cluver L. D., Orkin F. M., Boyes M. E., Sherr L. (2014). Cash plus care. AIDS 28, S389–S397. 10.1097/QAD.0000000000000340
    1. Cluver L. D., Orkin F. M., Meinck F., Boyes M. E., Sherr L. (2016). Structural drivers and social protection: mechanisms of HIV risk and HIV prevention for South African adolescents. J. Int. AIDS Soc. 19:20646. 10.7448/IAS.19.1.20646
    1. Conn V. S., Ruppar T. M. (2017). Medication adherence outcomes of 771 intervention trials: systematic review and meta-analysis. Prev. Med. 99, 269–276. 10.1016/j.ypmed.2017.03.008
    1. Cook R. L., Sereika S. M., Hunt S. C., Woodward W. C., Erlen J. A., Conigliaro J. (2001). Problem drinking and medication adherence among persons with HIV infection. J. Gen. Intern. Med. 16, 83–88. 10.1111/j.1525-1497.2001.00122.x
    1. Ebuy H., Yebyo H., Alemayehu M. (2015). Level of adherence and predictors of adherence to the Option B+ PMTCT programme in Tigray, northern Ethiopia. Int. J. Infect. Dis. 33, 123–129. 10.1016/j.ijid.2014.12.026
    1. Elovainio M., Hakulinen C., Pulkki-Råback L., Virtanen M., Josefsson K., Jokela M., et al. . (2017). Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study. Lancet Public Heal. 2, e260–e266. 10.1016/S2468-2667(17)30075-0
    1. Fernandes R. M., Cary M., Duarte G., Jesus G., Alarcão J., Torre C., et al. . (2017). Effectiveness of needle and syringe programmes in people who inject drugs – An overview of systematic reviews. BMC Public Health 17:309. 10.1186/s12889-017-4210-2
    1. Flanigan T. P., Mitty J. A. (2006). The good, the bad, and the ugly: providing highly active antiretroviral therapy when it is most difficult. Clin. Infect. Dis. 42, 1636–1638. 10.1086/503916
    1. Ford N., Nachega J. B., Engel M. E., Mills E. J. (2009). Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials. Lancet 374, 2064–2071. 10.1016/S0140-6736(09)61671-8
    1. Galvan F. H., Bing E. G., Fleishman J. A., London A. S., Caetano R., Burnam M. A., et al. . (2002). The prevalence of alcohol consumption and heavy drinking among people with HIV in the United States: results from the HIV Cost and Services Utilization Study. J. Stud. Alcohol. 63, 179–186. 10.15288/jsa.2002.63.179
    1. Gifford A. L., Bormann J. E., Shively M. J., Wright B. C., Richman D. D., Bozzette S. A. (2000). Predictors of self-reported adherence and plasma HIV concentrations in patients on multidrug antiretroviral regimens. J. Acquir. Immune Defic. Syndr. 23, 386–395. 10.1097/00042560-200004150-00005
    1. Gimeno-Gracia M., Crusells-Canales M. J., Javier Armesto-Gómez F., Rabanaque-Hernández M. J. (2015). Prevalence of concomitant medications in older HIV+ patients and comparison with general population. HIV Clin. Trials. 16, 117–124. 10.1179/1528433614Z.0000000012
    1. Gokarn A., Narkhede M. G., Pardeshi G. S., Kondiba M., Doibale. (2012). Adherence to antiretroviral therapy. J. Assoc. Phys. India 60, 16–20.
    1. Golrokhy R., Koochak H. E., Babaii A., Pourdast A., Rasoolinejad M., Moghadam S. R. J., et al. . (2017). Prevalence of Adverse Drug Reactions to Highly Active Antiretroviral Therapy (HAART) among HIV-Positive Patients in Imam Khomeini Hospital of Tehran, Iran. Infect. Disord. Drug Targets 17, 116–119. 10.2174/1871526517666170117111350
    1. Gonzalez A., Barinas J., O'Cleirigh C. (2011). Substance use: impact on adherence and HIV medical treatment. Curr. HIV/AIDS Rep. 8, 223–234. 10.1007/s11904-011-0093-5
    1. Graham S. M., Mugo P., Gichuru E., Thiong'o A., Macharia M., Okuku H. S., et al. . (2013). Adherence to antiretroviral therapy and clinical outcomes among young adults reporting high-risk sexual behavior, including men who have sex with men, in coastal kenya. AIDS Behav. 17, 1255–1265. 10.1007/s10461-013-0445-9
    1. Grossberg R., Gross R. (2007). Use of pharmacy refill data as a measure of antiretroviral adherence. Curr. HIV/AIDS Rep. 4, 187–191. 10.1007/s11904-007-0027-4
    1. Haberer J. E., Kahane J., Kigozi I., Emenyonu N., Hunt P., Martin J., et al. . (2010). Real-time adherence monitoring for HIV antiretroviral therapy. AIDS Behav. 14, 1340–1346. 10.1007/s10461-010-9799-4
    1. Haberer J. E., Sabin L., Amico K. R., Orrell C., Galárraga O., Tsai A. C., et al. . (2017). Improving antiretroviral therapy adherence in resource-limited settings at scale: a discussion of interventions and recommendations. J. Int. AIDS Soc. 20:21371. 10.7448/IAS.20.1.21371
    1. Hayashi K., Wood E., Kerr T., Dong H., Nguyen P., Puskas C. M., et al. . (2016). Factors associated with optimal pharmacy refill adherence for antiretroviral medications and plasma HIV RNA non-detectability among HIV-positive crack cocaine users: a prospective cohort study. BMC Infect. Dis. 16, 455. 10.1186/s12879-016-1749-y
    1. Hinkin C. H., Barclay T. R., Castellon S. A., Levine A. J., Durvasula R. S., Marion S. D., et al. . (2007). Drug use and medication adherence among HIV-1 infected individuals. AIDS Behav. 11, 185–194. 10.1007/s10461-006-9152-0
    1. Hinkin C. H., Hardy D. J., Mason K. I., Castellon S. A., Durvasula R. S., Lam M. N., et al. . (2004). Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse. AIDS 18(Suppl. 1), S19–S25.
    1. Horne R., Weinman J. (1999). Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J. Psychosom. Res. 47, 555–567. 10.1016/S0022-3999(99)00057-4
    1. Inciardi J. A. (1995). Crack, crack house sex, and HIV risk. Arch. Sex. Behav. 24, 249–269. 10.1007/BF01541599
    1. Johnson C. J., Heckman T. G., Hansen N. B., Kochman A., Sikkema K. J. (2009). Adherence to antiretroviral medication in older adults living with HIV/AIDS: a comparison of alternative models. AIDS Care 21, 541–551. 10.1080/09540120802385611
    1. Kalichman S. C., Ramachandran B., Catz S. (1999). Adherence to combination antiretroviral therapies in HIV patients of low health literacy. J. Gen. Intern. Med. 14, 267–273. 10.1046/j.1525-1497.1999.00334.x
    1. Kay E. S., Batey D. S., Mugavero M. J. (2016). The HIV treatment cascade and care continuum: updates, goals, and recommendations for the future. AIDS Res. Ther. 13, 35. 10.1186/s12981-016-0120-0
    1. Kelly C. M., van Oosterhout J. J., Ngwalo C., Stewart R. C., Benjamin L., Robertson K. R., et al. . (2014). HIV Associated Neurocognitive Disorders (HAND) in Malawian adults and effect on adherence to combination anti-retroviral therapy: a cross sectional study. PLoS ONE 9:e98962. 10.1371/journal.pone.0098962
    1. Kim S.-H., Gerver S. M., Fidler S., Ward H. (2014). Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis. AIDS 28, 1945–1956. 10.1097/QAD.0000000000000316
    1. Kirsten I., Sewangi J., Kunz A., Dugange F., Ziske J., Jordan-Harder B., et al. . (2011). Adherence to combination prophylaxis for prevention of mother-to-child-transmission of HIV in Tanzania. PLoS ONE 6:e21020. 10.1371/journal.pone.0021020
    1. Kumar V., Encinosa W. (2009). Effects of antidepressant treatment on antiretroviral regimen adherence among depressed HIV-infected patients. Psychiatr. Q. 80, 131–141. 10.1007/s11126-009-9100-z
    1. Lambers F. A. E., Stolte I. G., van den Berg C. H. S. B., Coutinho R. A., Prins M. (2011). Harm reduction intensity-Its role in HAART adherence amongst drug users in Amsterdam. Int. J. Drug Policy. 22, 210–218. 10.1016/j.drugpo.2011.02.004
    1. Langebeek N., Gisolf E. H., Reiss P., Vervoort S. C., Hafsteinsdóttir T. B., Richter C., et al. . (2014). Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis. BMC Med. 12:142. 10.1186/s12916-014-0142-1
    1. Liu A. Y., Hessol N. A., Vittinghoff E., Amico K. R., Kroboth E., Fuchs J., et al. . (2014). Medication adherence among men who have sex with men at risk for HIV infection in the united states: implications for pre-exposure prophylaxis implementation. AIDS Patient Care STDS 28, 622–627. 10.1089/apc.2014.0195
    1. Llibre J. M., Chien-Ching H., Brinson C., Castelli F., Wynn B., Vandermeulen K. A. M. (2017). Phase III Sword 1& 2: switch to DTG+RPV maintains virologic suppression through 48 Wks, in CROI Conference (Washington,DC: CROI Seattle; ), Abstract Number: 44LB.
    1. Macalino G. E., Hogan J. W., Mitty J. A., Bazerman L. B., DeLong A. K., Loewenthal H., et al. . (2007). A randomized clinical trial of community-based directly observed therapy as an adherence intervention for HAART among substance users. AIDS 21, 1473–1477. 10.1097/QAD.0b013e32811ebf68
    1. Margolis A. M., Heverling H., Pham P. A., Stolbach A. (2014). A review of the toxicity of HIV medications. J. Med. Toxicol. 10, 26–39. 10.1007/s13181-013-0325-8
    1. McCoy S. I., Strauss R. P., MacDonald P. D. M., Leone P. A., Eron J. J., Miller W. C. (2009). Social support and delays seeking care after HIV diagnosis, North Carolina, 2000-2006. AIDS Care 21, 1148–1156. 10.1080/09540120902730021
    1. Menezes de Pádua C. A., Moura C. S. (2014). Availability of data on adverse reactions to antiretroviral drugs in medical charts according to the naranjo algorithm: an example of a brazilian historical cohort. Clin. Drug Investig. 34, 395–402. 10.1007/s40261-014-0187-0
    1. Millar B. M., Starks T. J., Gurung S., Parsons J. T. (2017). The Impact of Comorbidities, depression, and substance use problems on quality of life among older adults living with, HIV. AIDS Behav. 21, 1684–1690. 10.1007/s10461-016-1613-5
    1. Mills E. J., Nachega J. B., Buchan I., Orbinski J., Attaran A., Singh S., et al. . (2006). Adherence to antiretroviral therapy in Sub-Saharan Africa and North America. JAMA 296, 679. 10.1001/jama.296.6.679
    1. Mountain E., Mishra S., Vickerman P., Pickles M., Gilks C., Boily M. (2014). Antiretroviral therapy uptake, attrition, adherence and outcomes among HIV-infected female sex workers: a systematic review and meta-analysis. PLoS ONE 9:e105645. 10.1371/journal.pone.0105645
    1. Nieuwkerk P. T., Sprangers M. A., Burger D. M., Hoetelmans R. M., Hugen P. W., Danner S. A., et al. . (2001). Limited patient adherence to highly active antiretroviral therapy for HIV-1 infection in an observational cohort study. Arch. Intern. Med. 161, 1962–1968. 10.1001/archinte.161.16.1962
    1. Orrell C., Cohen K., Leisegang R., Bangsberg D. R., Wood R., Maartens G. (2017). 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. 14, 20. 10.1186/s12981-017-0138-y
    1. Ortego C., Huedo-Medina T. B., Llorca J., Sevilla L., Santos P., Rodríguez E., et al. . (2011). Adherence to Highly Active Antiretroviral Therapy (HAART): a meta-analysis. AIDS Behav. 15, 1381–1396. 10.1007/s10461-011-9942-x
    1. Ortego C., Huedo-Medina T. B., Santos P., Rodrígue E., Sevilla L., Warren M., et al. . (2012). Sex differences in adherence to highly active antiretroviral therapy: a meta-analysis. AIDS Care 24, 1519–1534. 10.1080/09540121.2012.672722
    1. Paterson D. L., Swindells S., Mohr J., Brester M., Vergis E. N., Squier C., et al. . (2000). Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann. Intern. Med. 133, 21–30. 10.7326/0003-4819-133-1-200007040-00004
    1. Reblin M., Uchino B. N. (2008). Social and emotional support and its implication for health. Curr. Opin. Psychiatry 21, 201–205. 10.1097/YCO.0b013e3282f3ad89
    1. Samet J. H., Horton N. J., Meli S., Freedberg K. A., Palepu A. (2004). Alcohol consumption and antiretroviral adherence among HIV-infected persons with alcohol problems. Alcohol Clin. Exp. Res. 28, 572–577. 10.1097/01.ALC.0000122103.74491.78
    1. Shi L., Liu J., Koleva Y., Fonseca V., Kalsekar A., Pawaskar M. (2010). Concordance of adherence measurement using self-reported adherence questionnaires and medication monitoring devices. Pharmacoeconomics 28, 1097–1107. 10.2165/11537400-000000000-00000
    1. Sidat M., Fairley C., Grierson J. (2007). Experiences and perceptions of patients with 100% adherence to highly active antiretroviral therapy: a qualitative study. AIDS Patient Care STDS 21, 509–520. 10.1089/apc.2006.0201
    1. Spire B., Lucas G. M., Carrieri M. P. (2007). Adherence to HIV treatment among IDUs and the role of opioid substitution treatment (OST). Int. J. Drug Policy 18, 262–270. 10.1016/j.drugpo.2006.12.014
    1. Steiner J. F., Prochazka A V. (1997). The assessment of refill compliance using pharmacy records: methods, validity, and applications. J. Clin. Epidemiol. 50, 105–116. 10.1016/S0895-4356(96)00268-5
    1. Stirratt M. J., Dunbar-Jacob J., Crane H. M., Simoni J. M., Czajkowski S., Hilliard M. E., et al. . (2015). Self-report measures of medication adherence behavior: recommendations on optimal use. Transl. Behav. Med. 5, 470–482. 10.1007/s13142-015-0315-2
    1. Takada S., Weiser S. D., Kumbakumba E., Muzoora C., Martin J. N., Hunt P. W., et al. . (2014). The dynamic relationship between social support and HIV-related stigma in rural Uganda. Ann. Behav. Med. 48, 26–37. 10.1007/s12160-013-9576-5
    1. UNAIDS (2014). The Gap Report. UNAIDS.
    1. UNAIDS (2013). UNAIDS Report on the Global AIDS Epidemic 2013. UNAIDS.
    1. UNAIDS (2015). AIDS by the Numbers 2015. Available online at:
    1. Uthman O. A., Oladimeji O., Nduka C. (2017). Adherence to antiretroviral therapy among HIV-infected prisoners: a systematic review and meta-analysis. AIDS Care 29, 489–497. 10.1080/09540121.2016.1223799
    1. Viswanathan S., Detels R., Mehta S. H., Macatangay B. J. C., Kirk G. D., Jacobson L. P. (2015). Level of adherence and HIV RNA suppression in the current era of highly active antiretroviral therapy (HAART). AIDS Behav. 19, 601–611 10.1007/s10461-014-0927-4
    1. Vrijens B., De Geest S., Hughes D. A., Przemyslaw K., Demonceau J., Ruppar T., et al. . (2012). A new taxonomy for describing and defining adherence to medications. Br. J. Clin. Pharmacol. 73, 691–705. 10.1111/j.1365-2125.2012.04167.x
    1. Wagner G. J., Rabkin J. G. (2000). Measuring medication adherence: are missed doses reported more accurately than perfect adherence? AIDS Care 12, 405–408. 10.1080/09540120050123800
    1. Wanchu A., Kaur R., Bambery P., Singh S. (2007). Adherence to generic reverse transcriptase inhibitor-based antiretroviral medication at a Tertiary Center in North India. AIDS Behav. 11, 99–102. 10.1007/s10461-006-9101-y
    1. Wechsberg W. M., Golin C., El-Bassel N., Hopkins J., Zule W. (2012). Current interventions to reduce sexual risk behaviors and crack cocaine use among HIV-infected individuals. Curr. HIV/AIDS Rep. 9, 385–393. 10.1007/s11904-012-0131-y
    1. WHO (2001). Adherence to Long-term Therapies: Policy for Action. Meeting Report. Available online at:
    1. Wing E. J. (2016). HIV and aging. Int. J. Infect. Dis. 53, 61–68. 10.1016/j.ijid.2016.10.004
    1. Wohl D. A., Stephenson B. L., Golin C. E., Nichole Kiziah C., Rosen D., Ngo B., et al. . (2003). Adherence to directly observed antiretroviral therapy among human immunodeficiency virus–infected prison inmates. Clin. Infect. Dis. 36, 1572–1576. 10.1086/375076
    1. Wood E., Montaner J. S. G., Yip B., Tyndall M. W., Schechter M. T., O'Shaughnessy M V., et al. . (2003). Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users. CMAJ. 169, 656–661.
    1. Yun L. W. H., Maravi M., Kobayashi J. S., Barton P. L., Davidson A. J. (2005). Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients. J. Acquir. Immune. Defic. Syndr. 38, 432–438. 10.1097/01.qai.0000147524.19122.fd

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