- freely available
Diseases 2013, 1(1), 18-35; doi:10.3390/diseases1010018
Published: 13 September 2013
Abstract: The introduction of antiretroviral therapy (ART) in the management of HIV infection has resulted in a significant reduction in the morbidity and mortality associated with the disease. The fact that a nearly perfect adherence is required in ART has remained a major challenge to people infected with HIV. This review underscores the impact of adherence to antiretroviral therapy and highlights recent advances in adherence monitoring and enhancement among people infected with HIV who are on lifelong antiretroviral therapy.
Medical knowledge around HIV/AIDS has increased significantly over the years and good progress has been made in the treatment of HIV as a manageable life-threatening chronic condition using antiretroviral therapy (ART). The treatment of the disease extends beyond knowledge development among people infected with HIV; a partnership between them and healthcare providers is required, with the HIV-infected person assuming the major responsibility of self-care that will result in adherence and a good clinical outcome . This is the reason why medication adherence is described as the extent to which the individual’s behaviour corresponds to the prescribed medical advice of the health care provider . This review provides an overview on adherence to ART among people infected with HIV by describing the pattern of adherence to treatment. It also includes the consequences of non-adherence to treatment, and the barriers and facilitators of ART adherence. Furthermore, the various modalities of adherence monitoring and assessment are described in detail, together with recent advances in strategies and tools used in enhancing adherence to antiretroviral therapy.
Medication adherence is a major challenge in chronic medical condition. Adherence levels change over time. Clinical experience and research indicate that adherence is a “moving target”; the longer a patient stays on treatment the poorer the adherence is likely to become [3,4]. Generally, adherence rates are higher among patients who are taking medications for acute medical conditions compared to those with chronic medical conditions . In addition to this, adherence levels among patients with chronic diseases, no matter how impressive adherence is initially, have been reported to drop dramatically after six months . HIV-infected persons have been shown to adhere better than the general population; the average adherence to chronic medications among the general population is 50% which is far below the self-report adherence rate of between 55–77% among patients on ART . Despite this, non-adherence is common among patients on ART, which is estimated to be between 30–50%, and more than 10% of patients usually miss one or more of their daily doses of antiretroviral drugs . Adherence level among adolescents is usually lower than adults and elderly patients on ART [9,10]. In a study done in the USA among adolescents on antiretroviral drugs (ARVs), only 28% took all their prescribed ARVs in the previous month . Another cohort study in nine countries within the Southern Africa region also reported poor adherence among adolescents . A survey done among HIV patients in India also revealed poor adherence among people who were aged below 40 years . The explanatory factors responsible for this difference may be due to the fact that older individuals are more likely to have prior experience taking medication for age-related diseases and may have already become accustomed to such. Another reason may be related to the fact that lifestyle adjustments necessary for successful adherence are often less burdensome for adults compared to young patients .
Numerous interventional studies have been done in the past to address the problem of non-adherence among patients [6,12,13]. The unfortunate thing is that most of these interventions seem to have only modest impact [12,13,14]. The lack of appropriate theories to explain and predict non-adherence among patients on chronic medications may have a role to play in the slow progress made in developing interventions aimed at enhancing ART adherence [6,15].
6. Strategies and Tools for Enhancing Adherence
Adherence is very complex and unpredictable among patients on chronic medications; several methods of enhancing adherence exist in ART and are usually used in combination for better results. The interventions used in enhancing adherence among patients are aimed at addressing potential barriers to adherence.
6.2. Education and Counselling
This is usually the mainstay of ART programmes in any setting; Education and counsellingempowers the patient to be part of the treatment process. Knowledge about the disease, its symptoms, treatment and side-effects of the medications are crucial information that has to be passed on to the patient . During counselling, potential barriers to adherence are identified and addressed. Counselling assists the patient in developing positive beliefs and perception towards the disease . It also helps in setting goals and increases the self-efficacy of the patient . A randomized controlled trial in the USA to compare the effect of person-to-person contact and support adherence with medication alarm techniques revealed improved responses to therapy and good adherence among the group that received interpersonal adherence support . This finding is consistent with the literature where repeated supportive adherence has been described as the most effective intervention because it provides human contact and support .
6.3. Adherence Tools for Patients
These tools are often combined with other behavioural interventions . Pill boxes are containers used for storing the ARV for regular use as prescribed. They enable the patient to take the medication correctly. Electronic versions of pill boxes with reminders to the patient are also available. The major setback of this tool is the lack of confidentiality and privacy associated with it, since some patients do not want people around them to see their medications. Another setback is the task of filling out the boxes; uneducated patients might not be able to do this correctly. Pill charts involve visual display of the pills in terms of their colour, shape, name and dosage of the medication during counselling. This is very useful especially among the uneducated patients . Electronic devices such as beepers, alarms and watches that remind patients to take their medication according to the prescribed schedule are also used to enhance adherence . In addition, telephone calls and mobile-phone text messages have been shown to improve medication adherence in HIV infected individuals [85,86,87,88]. Electronic pagers linked to the internet may also be used to send reminders to patients to take their drugs. Although reminder tools have been reported by patients as one of the facilitators of adherence [85,86,87,88], the major disadvantage of this strategy is the lack of privacy associated with it. Another shortcoming is the cost required to set up this kind of service and the challenges associated with the patient having their mobile phones with them all the time . Medication diaries are very useful in understanding the patterns of drug use by the patient and the reasons for not taking the medication regularly. Diaries are used by the patients to document the time and date of taking the medications and missed doses and the reasons for it. This tool may also be used to identify side-effects or other problems that the patient may encounter in the course of taking ART. Research has shown that some tools appear to be of more benefit to patients when they are combined with patient education or counselling. A large multicenter randomized trial in the USA revealed that reminder devices alone do not enhance adherence and suggests that they should be combined with counselling as part of comprehensive support for patients on ART .
6.5. Health System and Service Delivery Interventions
These include interventions that target barriers to ART adherence at the level of health care delivery of HIV services such as food supplements, transportation to health facilities, staffing and integration of services. Research has demonstrated that ART adherence and retention in care are associated with interventions that offer food supplements, address transportation issues and integrated services. Family nutritional support for HIV positive patients on ART improves adherence leading to good clinical outcomes, and this could be integrated into ART adherence interventions as an effective and comprehensive community-based primary care . In a South African study, nurse-initiated ART services have been shown to produce the same outcomes as ART services run by doctors, which indicates that where human resources are limited, nurses can provide ART care . In addition, addressing the issue of transportation to the health facilities among HIV patients and integration of home-based care into ART services led to improved attendance in clinic appointments . ART regimens need to be chosen taking into consideration the patient’s working and family life, especially the cost implication of the drugs to ensure continuous supply so that adherence can be optimized .
Once initiated, antiretroviral therapy is a lifelong treatment; this has made adherence to ART one of the major challenges facing HIV/AIDS services following the rapid scale-up of ART to provide life-saving treatment to people infected with HIV. Non-adherence in ART is not limited to missing medication intake; it also includes other acts like not following instructions regarding dietary or fluid restrictions and not taking medication at the prescribed time. This underscores the complex nature of adherence in the management of HIV/AIDS as a chronic medical condition. Medication adherence is affected by patients’ beliefs about disease origin and transmission, which often form the basis for stigmatization in HIV/AIDS. Adequate knowledge of the medication and understanding the need for strict adherence, self-efficacy, sense of self-worth, acceptance of HIV status, making use of reminder tools and social support are factors that influence adherence to ART in different settings . Therefore, ART adherence needs to be tackled using a multi-disciplinary approach due to the difficultly in predicting which patients will adhere to treatment and those who will not; as a person’s past adherence is the only predictor of future adherence .
Conflicts of Interest
The authors declare no conflict of interest.
- Sanjobo, N.; Frich, J.C.; Fretheim, A. Barriers and facilitators to patients’ adherence to antiretroviral treatment in Zambia: a qualitative study. J. Soc. Asp. H 2008, 5, 136–143.
- Kenreigh, C.A.; Wagner, L.T. Medication adherence: A literature review. Medscape , 2005.
- Cauldbeck, M.; O’Connor, C.; O’Connor, M.; Saunders, J.; Rao, B.; Mallesh, V.; Kotechalappa, N.; Kumar, P.; Mamtha, G.; McGoldrick, C.; Laing, R.; Satish, S. Adherence to antiretroviral therapy among HIV patients in Bangalore, India. AIDS Res. Ther. 2009, 6, 7, doi:10.1186/1742-6405-6-7.
- Ickovics, J.R.; Meade, C.S. Adherence to antiretroviral therapy among patients with HIV: A critical link between behavioural and biomedical sciences. J. Acq. Immun. Def. Synd. 2002, 31, S98–S102, doi:10.1097/00126334-200212153-00002.
- McDonald, H.P.; Garg, A.X.; Haynes, R.B. Interventions to enhance patient adherence to medication prescriptions. JAMA 2002, 288, 2868–2879, doi:10.1001/jama.288.22.2868.
- Van Dulmen, S.; Sluijs, E.; van Dijk, L.; de Riddet, D.; Heerdink, R.; Bensing, J. Patient adherence to medical treatment: a review of reviews. BMC Health Serv. Res. 2007, 7, 55, doi:10.1186/1472-6963-7-55.
- Mills, E.J.; Nachega, J.B.; Buchan, I.; Orbinski, J.; Attaran, A.; Singh, S.; Rachlis, B.; Wu, P.; Cooper, C.; Thabane, L.; et al. Adherence to antiretroviral therapy in sub-Saharan Africa and North America: A meta-analysis. JAMA 2006, 296, 679–690, doi:10.1001/jama.296.6.679.
- Chesney, M.A. Factors affecting adherence to antiretroviral therapy. Clin. Infect. Dis. 2000, 30, S171–S176, doi:10.1086/313849.
- Protopopescu, C.; Raffi, F.; Roux, P.; Reynes, J.; Dellamonica, P.; Spire, B.; Leport, C.; Carrieri, M.; and on behalf of the ANRS CO8 (APROCO-COPILOTE) Study Group. Factors associated with non-adherence to long-term highly active antiretroviral therapy: a 10-year follow-up analysis with correction for the bias induced by missing data. J. Antimicrob. Chemoth. 2009, 64, 599–606, doi:10.1093/jac/dkp232.
- Murphy, D.A.; Sarr, M.; Durako, S.J.; Moscicki, A.; Wilson, C.M.; Muenz, L.R.; for the Adolescent Medicine HIV/AIDS Research Network. Barriers to HAART adherence among HIV-infected adolescents. Arch. Pediatr. Adolesc. Med. 2003, 157, 249–255, doi:10.1001/archpedi.157.3.249.
- Nachega, J.; Hislop, M.; Nguyen, H.; Dowdy, D.; Regensberg, L.; Chaisson, R.; Cotton, M.; Maartens, G. Antiretroviral therapy adherence, Virologic and immunologic outcomes in adolescents compared with adults in Southern Africa. J. Acq. Immun. Def. Synd. 2009, 51, 65–71, doi:10.1097/QAI.0b013e318199072e.
- Amico, K.R.; Harman, J.J.; Johnson, B.T. Efficacy of antiretroviral therapy adherence interventions a research synthesis of trials, 1996 to 2004. J. Acq. Immun. Def. Synd. 2006, 41, 285–297, doi:10.1097/01.qai.0000197870.99196.ea.
- Munro, S.; Lewin, S.; Swart, T.; Volmink, J. A review of health behaviour theories: how useful are these for developing interventions to promote long-term medication adherence for TB and HIV/AIDS. BMC Public Health 2007, 7, 104, doi:10.1186/1471-2458-7-104.
- Simoni, J.M.; Frick, P.A.; Pantalone, D.W.; Turner, B.J. Antiretroviral adherence interventions: A review of current literature and ongoing studies. Top. HIV Med. 2003, 11, 185–198.
- Kagee, A. Adherence to antiretroviral therapy in the context of the national roll-out in South Africa: Defining a research agenda for psychology. S Afr. J. Psychol. 2008, 38, 413–428.
- Paterson, D.L.; Swindells, S.; Mohr, J.; Brester, M.; Vergis, E.N.; Squier, C.; Wagener, M.M.; Singh, N. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann. Intern. Med. 2000, 133, 21–30.
- Bangsberg, D.R.; Moss, A.R.; Deeks, S.G. Paradoxes of adherence and drug resistance to HIV antiretroviral therapy. J. Antimicrob. Chemoth. 2004, 53, 696–699, doi:10.1093/jac/dkh162.
- Clotet, B. Strategies for overcoming resistance in HIV-1 infected patients receiving HAART. AIDS Reviews 2004, 6, 123–130.
- Gazzard, B.G; on behalf of the BHIVA Treatment Guidelines Writing Group. British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV Medicine 2008, 9, 563–608, doi:10.1111/j.1468-1293.2008.00636.x.
- Thompson, M.; Aberg, J.; Cahn, P.; Montaner, J.; Rizzardini, G.; Telenti, A.; Gatell, J.M.; Günthard, H.; Hammer, S.; Hirsch, M.; et al. Antiretroviral treatment of adult HIV infection: 2010 Recommendations of the International AIDS Society—USA Panel. JAMA 2010, 304, 321–333, doi:10.1001/jama.2010.1004.
- Nachega, J.B.; Hislop, M.; Dowdy, D.W.; Chaisson, R.E.; Regensberg, L.; Maartens, G. Adherence to non-nucleoside reverse transcriptase inhibitor-based HIV therapy and virologic outcomes. Ann. Intern. Med. 2007, 146, 564–573, doi:10.7326/0003-4819-146-8-200704170-00007.
- Bangsberg, D.R. Less than 95% adherence to nucleoside reverse transcriptase inhibitors therapy can lead to viral suppression. Clin. Infect. Dis. 2006, 43, 939–941, doi:10.1086/507526.
- Weiser, S.; Wolfe, W.; Bangsberg, D.; Thior, I.; Gilbert, P.; Makhema, J.; Kebaabetswe, P.; Dickenson, D.; Mompati, K.; Essex, M.; et al. Barriers to antiretroviral adherence for patients living with HIV infection and AIDS in Botswana. J. Acq. Immun. Def. Synd. 2003, 34, 281–288, doi:10.1097/00126334-200311010-00004.
- Amberbir, A.; Woldemichael, K.; Getachew, S.; Girma, B.; Deribe, K. Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in southwest Ethiopia. BMC Public Health 2008, 8, 268, doi:10.1186/1471-2458-8-268.
- Uzochukwu, B.S.C.; Onwujekwe, O.E.; Onoka, A.C.; Okoli, C.; Uguru, N.P.; Chukwuogo, O.I. Determinants of non-adherence to subsidized antiretroviral treatment in southeast Nigeria. Health Policy Plan. 2009, 24, 189–196, doi:10.1093/heapol/czp006.
- Peltzer, K.; du Preez, N.; Ramlagan, S.; Anderson, J. Antiretroviral treatment adherence among HIV patients in KwaZulu-Natal, South Africa. BMC Public Health 2010, 10, 111, doi:10.1186/1471-2458-10-111.
- Malangu, N.G. Self-reported adverse effects as barriers to adherence to antiretroviral therapy in HIV-infected patients in Pretoria. SA Fam. Pract. 2008, 50, 49.
- Janssens, B.; Raleigh, B.; Soeung, S.; Akao, K.; Te, V.; Gupta, J.; Chhy Vun, M.; Ford, N.; Nouhin, J.; Nerrienet, E. Effectiveness of highly active antiretroviral therapy in HIV-positive children: Evaluation at 12 Months in a routine program in Cambodia. Pediatrics 2007, 120, e1134–e1140, doi:10.1542/peds.2006-3503.
- Duong, M.; Golzi, A.; Peytavin, G.; Piroth, L.; Froidure, M.; Grappin, M.; Buisson, M.; Kohli, E.; Chavanet, P.; Portier, H. Usefulness of therapeutic drug monitoring of antiretroviral in routine clinical practice. HIV Clin. Trials 2004, 5, 216–223, doi:10.1310/NXJU-9ERQ-ADWW-UC5X.
- Ware, N.C.; Idoko, J.; Kaaya, S.; Biraro, I.A.; Wyatt, M.A.; Agbaji, O.; Chalamilla, G.; Bangsberg, D.R. Explaining adherence success in sub-Saharan Africa: an ethnographic study. PLOS Med. 2009, 6, e1000011.
- Bangsberg, D.R.; Charlebois, E.D.; Grant, R.M.; Holodniy, M.; Deeks, S.G.; Perry, S.; Conroy, K.N.; Clark, R.; Guzman, D.; Zolopa, A.; et al. High levels of adherence do not prevent accumulation of drug resistance mutations. AIDS 2003, 17, 1925–1932, doi:10.1097/00002030-200309050-00011.
- Nachega, J.B.; Hislop, M.; Dowdy, D.W.; Lo, M.; Omer, S.B.; Regensberg, L.; Chaisson, R.E.; Maartens, G. Adherence to highly active antiretroviral therapy assessed by pharmacy claims predicts survival in HIV-infected South African adults. J. Acq. Immun. Def. Synd. 2006, 43, 78–84, doi:10.1097/01.qai.0000225015.43266.46.
- Rubbert, A.; Behrens, G.; Ostrowski, M. Ch 4—Pathogenesis of HIV-1 infection. In HIV Medicine; Hoffman, C., Rockstroh, J., Kamps, B., Eds.; Flying Publisher: Paris, France, 2007; pp. 59–81.
- Graham, S.M.; Masese, L.; Gitau, R.; Jalalian-Lechak, Z.; Richardson, B.A.; Peshu, N.; Mandaliya, K.; Kiarie, J.N.; Jaoko, W.; Ndinya-Achola, J.; et al. Antiretroviral adherence and development of drug resistance are the strongest predictors of genital HIV-1 shedding among women initiating treatment. J. Infect. Dis. 2010, 201, 1538–1542.
- Moore, D.M.; Hogg, R.S.; Yip, B.; Wood, E.; Tyndall, M.; Braitstein, P.; Montaner, J.S. Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J. Acq. Immun. Def. Synd. 2005, 40, 288–293, doi:10.1097/01.qai.0000182847.38098.d1.
- Wools-Kaloustian, K.; Kimayo, S.; Diero, L.; Siika, A.; Sidle, J.; Yiannoustsos, T.; Musick, B.; Einterz, R.; Fife, K.; Tierney, W. Viability and effectiveness of large-scale HIV treatment initiatives in Sub-Saharan Africa: experience from western Kenya. AIDS 2006, 20, 41–48, doi:10.1097/01.aids.0000196177.65551.ea.
- Boyd, M.; Pett, S. HIV fusion inhibitors: a review. Aust. Prescr. 2008, 31, 66–69.
- Hogg, R.S.; Heath, K.; Bangsberg, D.; Yip, B.; Press, N.; O'Shaughnessy, M.V.; Montaner, J.S. Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. AIDS 2002, 16, 1051–1058, doi:10.1097/00002030-200205030-00012.
- de Olalla, P.G.; Knobel, H.; Carmona, A.; Guelar, A.; Lopez-Colomes, J.L.; Cayla, J.A. Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients. J. Acq. Immun. Def. Synd. 2002, 30, 105–110.
- Dahab, M.; Charalambous, S.; Hamilton, R.; Fielding, K.; Kielmann, K.; Churchyard, G.J.; Grant, A.D. “That is why I stopped the ART”: patients’ and providers’ perspectives on barrier to and enablers of HIV treatment adherence in a South African workplace programme. BMC Public Health 2008, 8, 63, doi:10.1186/1471-2458-8-63.
- Curioso, W.H.; Kepka, D.; Cabello, R.; Segura, P.; Kurth, A.E. Understanding the facilitators and barriers of antiretroviral adherence in Peru: a qualitative study. BMC Public Health 2010, 10, 13, doi:10.1186/1471-2458-10-13.
- San Lio, M.M.; Carbini, R.; Germano, P.; Guidotti, G.; Mancinelli, S.; Magid, N.A.; Narciso, P.; Palombi, L.; Renzi, E.; Zimba, I.; et al. Evaluation of adherence to highly active antiretroviral therapy with use of pills counts and viral load measurement in the drug resources enhancement against AIDS and malnutrition program in Mozambique. Clin. Infect. Dis. 2008, 46, 1609–1616, doi:10.1086/587659.
- Hardon, A.P.; Akurut, D.; Comoro, C.; Ekezie, C.; Irunde, H.F.; Gerrits, T.; Kglatwane, J.; Kinsman, J.; Kwasa, R.; Maridadi, J.; et al. Hunger, Waiting time and transport costs: Time to confront challenges to ART adherence in Africa. AIDS Care 2007, 19, 658–665, doi:10.1080/09540120701244943.
- Oyugi, J.H.; Byakika-Tusiime, J.; Charlebois, E.D.; Kityo, C.; Mugerwa, R.; Mugyenyi, P.; Bangsberg, D.R. Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting. J. Acq. Immun. Def. Synd. 2004, 36, 1100–1102, doi:10.1097/00126334-200408150-00014.
- Fox, M.P.; Rosen, S. Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: Systematic review. Trop. Med. Int. Health 2010, 15, 1–15.
- Montessori, V.; Press, N.; Harris, M.; Akagi, L.; Montaner, J. Adverse effects of antiretroviral therapy for HIV infection. Can. Med. Assoc. J. 2004, 170, 229–238.
- Orrell, C.; Bangsberg, D.R.; Badri, M.; Wood, R. Adherence is not a barrier to successful antiretroviral therapy in South Africa. AIDS 2003, 17, 1369–1375, doi:10.1097/00002030-200306130-00011.
- Rougemont, M.; Stoll, B.; Elia, N.; Ngang, P. Antiretroviral treatment adherence and its determinants in Sub-Saharan Africa: A prospective study at Yaoundé central hospital, Cameroon. AIDS Res. Ther. 2009, 6, 21, doi:10.1186/1742-6405-6-21.
- Gordillo, V.; del Amo, J.; Soriano, V.; Gonzalez-Lahoz, J. Socio-demographic and psychological variables influencing adherence to antiretroviral therapy. AIDS 1999, 13, 1763–1769, doi:10.1097/00002030-199909100-00021.
- Berg, K.M.; Cooperman, N.A.; Newville, H.; Arnsten, J.H. Self-efficacy and depression as mediators of the relationship between pain and antiretroviral adherence. AIDS Care 2009, 21, 244–248, doi:10.1080/09540120802001697.
- Howard, A.A.; Armsten, J.H.; Yuntai, L.; Vlahov, D.; Rich, J.D.; Schumand, P.; Stonee, V.E.; Smith, D.K.; Schoenbaum, E.E.; for HER study group. A prospective study of adherence and viral load in a large multi-centre cohort of HIV-infected women. AIDS 2002, 16, 2175–2182, doi:10.1097/00002030-200211080-00010.
- Glass, T.R.; Battegay, M.; Cavassini, M.; De Geest, S.; Furrer, H.; Vernazza, P.L.; Hirschel, B.; Bernasconi, E.; Rickenbach, M.; Günthard, H.F.; Bucher, H.C.; The Swiss HIV cohort study. Longitudinal analysis of patterns and predictors of changes in self-reported adherence to antiretroviral therapy: Swiss HIV Cohort Study. J. Acq. Immun. Def. Synd. 2010, 54, 197–203.
- Hawkins, C.; Murphy, R. Adherence to antiretroviral therapy in resource-limited settings: everything matters. AIDS 2007, 21, 1041–1042, doi:10.1097/QAD.0b013e3281900eb9.
- Iliyasu, Z.; Kabir, M.; Abubakar, I.S.; Babashani, M.; Zubair, Z.A. Compliance to antiretroviral therapy among AIDS patients in Aminu Kano Teaching Hospital, Kano, Nigeria. Niger J. Med. 2005, 14, 290–294.
- Mukhtar-Yola, M.; Adeleke, S.; Gwarzo, D.; Ladan, Z. Preliminary investigation of adherence to antiretroviral therapy among children in Aminu Kano Teaching Hospital, Nigeria. AJAR 2006, 5, 141–144, doi:10.2989/16085900609490374.
- Tuller, D.M.; Bangsberg, D.R.; Senkungu, J.; Ware, N.C.; Emenyonu, N.; Weiser, S.D. Transportation costs impede sustained adherence and access to HAART in a clinic population in Southwestern Uganda. AIDS Behav. 2009, 14, 778–784.
- Castro, A. Adherence to antiretroviral therapy: merging the clinical and social course of AIDS. PLoS Med. 2005, 2, e338, doi:10.1371/journal.pmed.0020338.
- Nachega, J.B.; Stein, D.M.; Lehman, D.A.; Hlatshwayo, D.; Mothopeng, R.; Chaisson, R.E.; Karstaedt, A.S. Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa. AIDS Res. Hum. Retroviruses 2004, 20, 1053–1056, doi:10.1089/aid.2004.20.1053.
- Garcia, R.; Badaro, R.; Netto, E.; Silva, M.; Amorin, F.; Ramos, A.; Vaida, F.; Brites, C.; Schooley, R. Cross-sectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients. AIDS Res. Hum. Retroviruses 2006, 22, 1248–1252, doi:10.1089/aid.2006.22.1248.
- Mukherjee, J.S.; Ivers, L.; Leandre, F.; Farmer, P.; Behforouz, H. Antiretroviral therapy in resource-poor settings: Decreasing barriers to access and promoting adherence. J. Acq. Immun. Def. Synd. 2006, 43, S123–S126, doi:10.1097/01.qai.0000248348.25630.74.
- Frank, I. Once-daily HAART: toward a new treatment paradigm. J. Acq. Immun. Def. Synd. 2002, 31, S10–S15, doi:10.1097/00126334-200209011-00003.
- Roca, B.; Lapuebula, C.; Vidal-Tregedor, B. HAART with didanosine once versus twice daily: adherence and efficacy. Int. J. Infect. Dis. 2005, 9, 195–200, doi:10.1016/j.ijid.2004.07.006.
- Waters, L.; Nelson, M. Why do patients fail HIV therapy? Int. J. Clin. Pract. 2007, 61, 983–990, doi:10.1111/j.1742-1241.2007.01383.x.
- Harries, A.D.; Zachariah, R.; Lawn, S.D.; Rosen, S. Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa. Trop. Med. Int. Health 2010, 15, 70–75, doi:10.1111/j.1365-3156.2010.02506.x.
- Parienti, J.J.; Bangsberg, D.R.; Verdon, R.; Gardner, E.M. Better adherence with once-daily antiretroviral regimens: A meta-analysis. Clin. Infect. Dis. 2009, 48, 484–488, doi:10.1086/596482.
- Gauchet, A.; Tarquinio, C.; Fischer, G. Psychosocial predictors of medication adherence among persons living with HIV. Int. J. Behav. Med. 2007, 3, 141–150, doi:10.1007/BF03000185.
- Altice, F.L.; Mostashari, F.; Friedland, G.H. Trust and acceptance of and adherence to antiretroviral therapy. J. Acq. Immun. Def. Synd. 2001, 28, 47–58.
- Simoni, J.M.; Pearson, C.R.; Pantalone, D.W.; Marks, G.; Crepaz, N. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load: A meta-analytic review of randomized controlled trials. J. Acq. Immun. Def. Synd. 2006, 43, S23–S35, doi:10.1097/01.qai.0000248342.05438.52.
- Julius, R.J.; Novitsky, M.A.; Dubin, W.R. Medication adherence: a review of the literature and implications for clinical practice. J. Psychiatr. Pract. 2009, 15, 34–44, doi:10.1097/01.pra.0000344917.43780.77.
- Colebunders, R.; Moses, K.R.; Laurence, J.; Shihab, H.M.; Semitala, F.; Lutwama, F.; Bakeera-Kitaka, S.; Lynen, L.; Spacek, L.; Reynolds, S.J.; et al. A new model to monitor the virological efficacy of antiretroviral treatment in resource poor countries. Lancet Infect. Dis. 2006, 6, 53–59, doi:10.1016/S1473-3099(05)70327-3.
- Kouanfack, C.; Laurent, C.; Peytavin, G.; Ciaffi, L.; Ngolle, M.; Nkene, Y.M.; Essomba, C.; Calmy, A.; Mpoudi-Ngole, E.; Delaporte, E.; et al; the French national agency for research on AIDS 1274 study group. Adherence to antiretroviral therapy assessed by drug level monitoring and self-reports in Cameroon. J. Acq. Immun. Def. Synd. 2008, 48, 216–219, doi:10.1097/QAI.0b013e3181743955.
- Ross-Degnan, D.; Pierre-Jacques, M.; Zhang, F.; Tadeg, H.; Gitau, L.; Ntaganira, J.; Balikuddembe, R.; Chalker, J.; Wagner, A.K.; INRUD IAA7. Measuring adherence to antiretroviral treatment in resource poor settings: the clinical validity of key indicators. BMC Health Serv. Res. 2010, 10, 42, doi:10.1186/1472-6963-10-42.
- Bell, D.J.; Kapitao, Y.; Sikwese, R.; van Oosterhout, J.J.; Lallo, D.G. Adherence to antiretroviral therapy in patients receiving free treatment from a government hospital in Blantyre, Malawi. J. Acq. Immun. Def. Synd. 2007, 45, 560–563, doi:10.1097/QAI.0b013e3180decadb.
- Bova, C.A.; Fennie, K.P.; Knafi, G.J.; Dieckhaus, K.D.; Watrous, E.; Williams, A.B. Use of electronic monitoring devices to measure antiretroviral adherence: practical considerations. AIDS Behav. 2005, 9, 103–110, doi:10.1007/s10461-005-1685-0.
- Wilson, D.; Keiluhu, A.K.; Kogrum, S.; Reid, T.; Seriratana, N.; Ford, N.; Kyawkyaw, M.; Talangsri, P.; Taochalee, N. HIV-1 viral load monitoring: an opportunity to reinforce treatment adherence in a resource-limited setting in Thailand. T Roy. Soc. Trop. Med. H 2009, 103, 601–606, doi:10.1016/j.trstmh.2008.11.007.
- Birbeck , G.L.; Chomba, E.; Kvalsund, M.; Bradbury, R.; Mang’ombe, M.; Malama, K.; Kail, T.; Byers, P.A.; Organek, N.; for the RAAZ Study Team. Antiretroviral adherence in rural Zambia: The first year of treatment availability. Am. J. Trop. Med. Hyg. 2009, 80, 669–674.
- Kauf, T.L.; Davis, K.L.; Earnshaw, S.R.; Davis, E.A. Spillover adherence effects of fixed-dose combination HIV therapy. Patient Prefer. Adherence 2012, 6, 155–164.
- Haberer, J.E.; Cook, A.; Walker, A.S.; Ngambi, M.; Ferrier, A.; Mulenga, V.; Kityo, C.; Thomason, M.; Kabamba, D.; Chintu, C.; et al. Excellent adherence to antiretroviral in HIV+ Zambian children is compromised by disrupted routine, HIV nondisclosure, and paradoxical income effects. PLoS ONE 2011, 6, e18505, doi:10.1371/journal.pone.0018505.
- Nachega, J.B.; Knowlton, A.R.; Deluca, A.; Schoeman, J.H.; Watkinson, L.; Efron, A.; Chaisson, R.E.; Maartens, G. Treatment supporter to improve adherence to antiretroviral therapy in HIV-infected South African adults: a qualitative study. J. Acq. Immun. Def. 2006, 43, S127–S133, doi:10.1097/01.qai.0000248349.25630.3d.
- Magadza, C.; Radloff, S.E.; Srinivas, S.C. The effect of an educational intervention on patients’ knowledge about hypertension, beliefs about medicines, and adherence. Res. Social Adm. Pharm. 2009, 5, 363–375, doi:10.1016/j.sapharm.2009.01.004.
- Barclay, T.R.; Hinkin, C.H.; Castellon, S.A.; Mason, K.I.; Reinhard, M.J.; Marion, S.D.; Levine, A.J.; Durvasula, R.S. Age-associated predictors of medication adherence in HIV-positive adults: health beliefs, self-efficacy and neurocognitive status. Health Psychol. 2007, 26, 40–49, doi:10.1037/0278-6220.127.116.11.
- Johnson, M.O.; Charlebois, E.; Morin, S.F.; Remien, R.H.; Chesney, M.A.; The NIMH Healthy Living Project Team. Effects of a behavioural intervention on antiretroviral medication adherence among people living with HIV: The Healthy Living Project randomized controlled study. J. Acq. Immun. Def. Synd. 2007, 46, 574–580, doi:10.1097/QAI.0b013e318158a474.
- Mannheimer, S.B.; Morse, E.; Matts, J.P.; Andrews, L.; Child, C.; Schmetter, B.; Friedland, G.H.; (For the Terry Beirn community programs for clinical research on AIDS). Sustained benefit from a long-term antiretroviral adherence intervention: Results of a large randomized clinical trial. J. Acq. Immun. Def. Synd. 2006, 43, S41–S47, doi:10.1097/01.qai.0000245887.58886.ac.
- Saberi, P.; Johnson, M.O. Technology-based self-care methods of improving antiretroviral adherence: A systematic review. PLoS ONE 2011, 6, e27533, doi:10.1371/journal.pone.0027533.
- Bärnighausen, T.; Chaiyachati, K.; Chimbindi, N.; Peoples, A.; Haberer, J.; Newell, M.L. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies. Lancet Infect. Dis. 2011, 11, 942–951, doi:10.1016/S1473-3099(11)70181-5.
- Van Velthoven, M.H.; Brusamento, S.; Majeed, A.; Car, J. Scope and effectiveness of mobile phone messaging for HIV/AIDS care: a systematic review. Psychol. Health Med. 2013, 18, 182–202, doi:10.1080/13548506.2012.701310.
- Rodrigues, R.; Shet, A.; Antony, J.; Sidney, K.; Arumugam, K.; Krishnamurthy, S.; D’Souza, G.; DeCosta, A. Supporting Adherence to Antiretroviral Therapy with Mobile Phone Reminders: Results from a Cohort in South India. PLoS ONE 2012, 7, e40723, doi:10.1371/journal.pone.0040723.
- Skinner, D.; Rivette, U.; Bloomberg, D. Evaluation of use of cellphones to aid compliance with drug therapy for HIV patients. AIDS Care 2007, 19, 605–607, doi:10.1080/09540120701203378.
- Clarke, M.; Dick, J.; Zwarenstein, M.; Lombard, C.J.; Diwan, V.K. Lay health worker intervention with choice of DOT superior to standard TB care for farm dwellers in South Africa: a cluster randomized control trial. Int. J. Tuber. Lung Dis. 2005, 9, 673–679.
- Manders, A.J.; Banerjee, A.; van den Borne, H.W.; Harries, A.D.; Kok, G.J.; Salaniponi, F.M. Can guardians supervise TB treatment as well as health workers? A study on adherence during the intensive phase. Int. J. Tuber. Lung Dis. 2001, 9, 838–842.
- Wilkinson, D.; Davies, G.R.; Connolly, C. Directly observed therapy for tuberculosis in rural South Africa, 1991 through 1994. Am. J. Public Health 1996, 86, 1094–1097, doi:10.2105/AJPH.86.8_Pt_1.1094.
- Farmer, P.; Leandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J.Y. Community-based treatment of advance HIV disease: Introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy). Bull. World Health Organ. 2001, 79, 1145–1151.
- Lucas, G.M.; Flexner, C.W.; Moore, R.D. Directly administered antiretroviral therapy in the treatment of HIV infection: benefit or burden? AIDS Patient Care STDS 2002, 16, 527–535, doi:10.1089/108729102761041083.
- Sarna, A.; Lutchers, S.; Giebel, S.; Chersich, M.F.; Munyao, P.; Kaai, S.; Mandaliya, K.N.; Shikely, K.S.; Temmerman, M.; Rutenberg, N. Short and long term efficacy of modified directly observed antiretroviral treatment Mombasa, Kenya: a randomized trial. J. Acq. Immun. Def. Synd. 2008, 48, 611–619, doi:10.1097/QAI.0b013e3181806bf1.
- Serrano, C.; Laporte, R.; Ide, M.; Nouhou, Y.; Truchis, P.; Rouveix, E.; Adamou, A.; Pauly, V.; Mattei, J.F.; Gastaut, J.A. Family nutritional support improves survival, immune restoration and adherence in HIV patients receiving ART in developing country. Asia Pac. J. Clin. Nutr. 2010, 19, 68–75.
- Sanne, I.; Orrell, C.; Fox, M.P.; Conradie, F.; Ive, P.; Zeinecker, J.; Cornell, M.; Heiberg, C.; Ingram, C.; Panchia, R.; et al; for CIPRA-SA Study Team. Nurse versus doctor management of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomized non-inferiority trial. Lancet 2010, 376, 33–40, doi:10.1016/S0140-6736(10)60894-X.
- Andersen, M.; Hockman, E.; Smereck, G.; Tinsley, J.; Milfort, D.; Wilcox, R.; Smith, T.; Connelly, C.; Adams, L.; Thomas, R. Retaining women in HIV medical care. J. Assoc. Nurse AIDS C 2007, 18, 33–41, doi:10.1016/j.jana.2007.03.007.
- Volberding, P.A.; Deeks, S.G. Antiretroviral therapy and management of HIV infection. Lancet 2010, 376, 49–62, doi:10.1016/S0140-6736(10)60676-9.
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