Epidemiology & Social: Concise Communication
Doubts about DOT: antiretroviral therapy for resource-poor countries
Liechty, Cheryl A; Bangsberg, David R
From the the Epidemiology and Prevention Interventions Center, Division of Infectious Diseases, and the San Francisco General Hospital AIDS Program, San Francisco General Hospital, UCSF, and The Academic Alliance, Kampala, Uganda.
Correspondence to D. Bangsberg, EPI Center, RM 301, Building 100, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, California 94110, USA.
Received: 8 July 2002; revised: 11 October 2002; accepted: 22 January 2003.
Introduction: Directly observed therapy programs developed for tuberculosis (TB) have been suggested as a model for the provision of HIV medications in resource-poor countries in order to ensure adherence and prevent drug resistance.
Methods: Opinions were formed based on a review of scientific literature regarding the effectiveness of witnessed dosing in directly observed TB therapy programs, adherence to HIV antiretroviral therapy in resource-rich and resource-poor settings, relationship between adherence and HIV antiretroviral drug resistance, HIV viral load and risk of HIV transmission, and stigmatization concerns related to HIV and TB in resource-poor settings.
Results/conclusions: We suggest that the enthusiasm for HIV directly observed therapy programs is premature based on: equivocal evidence that witnessed dosing is superior to self administered therapy; mistaken assumptions that resource-poor countries are a ‘special case’ with respect to adherence; possible paradoxical impact of good adherence on HIV drug resistance; unproven efficacy of antiretroviral therapy in preventing HIV transmission; and potential stigmatization of daily antiretroviral dosing.
Recent price reductions and the introduction of ‘off-patent’ antiretroviral medications bring new hope that HIV antiretroviral treatment may be more widely available in resource-poor countries where over 90% of HIV infections occur . Many believe that poor adherence to antiretroviral therapy will accelerate widespread drug resistance in Africa, [2–4] and some believe that treatment should be delayed until we can ensure adherence . Will ‘widespread, unregulated access to antiretroviral drugs in sub-Saharan Africa lead to the rapid emergence of drug resistant viral strains, spelling doom for the individual, curtailing future treatment options, and [lead] to transmission of resistant virus', as has been suggested?  Based on these concerns, directly observed therapy programs for tuberculosis (TB) have been proposed as a model for the provision of HIV medications in resource-poor countries to ensure adherence and prevent drug resistance [2,6–11].
We believe that calls for directly observed therapy programs to provide routine HIV care are premature. Witnessed dosing has unclear efficacy in improving adherence and reducing HIV transmission, and may paradoxically promote drug resistance. Furthermore, requiring directly observed therapy may impose substantial barriers to antiretroviral access in resource-poor countries.
Experience with directly observed therapy and TB
Enthusiasm for directly observed HIV therapy is based on experience with TB treatment . The WHO began to promote Directly Observed Treatment, Short-course (DOTS) worldwide in 1993 . DOTS is a multifaceted approach to TB control, where observed pill-taking is just one component. Community and local government commitment, case detection by sputum smear microscopy, stable drug supply, and standardized systems for case follow-up are essential activities of successful DOTS programs. The success of DOTS has been documented by observational studies in numerous settings [14–17].
While these observational studies suggest that DOTS programs achieve higher cure rates than historical controls, the impact of witnessed therapy has rarely been isolated from other components of the DOTS strategy. Only three randomized trials in resource-poor countries have compared witnessed dosing with self-administered therapy. A South African study found self-administered therapy was equivalent to clinic-based directly observed therapy . In Thailand, directly observed therapy was superior to self-administered therapy in rural but not urban settings . In Pakistan, clinic-based directly observed therapy, family administered directly observed therapy, and self-administered therapy were equivalent [20,21]. As has been argued elsewhere, the success of TB control programs depends more on the strength of diverse structural components, including reliable drug supply and distribution, than solely on witnessed dosing .
Evidence that directly observed therapy improves HIV treatment outcomes
Experience with directly observed therapy to treat HIV is limited. Comparing two non-randomized cohorts of prisoners, Fischl found that 100% of those receiving directly observed therapy achieved viral suppression to < 400 HIV RNA copies/ml plasma, compared to 81% of those receiving self-administered therapy . Encouraging rates of viral suppression have also been observed in a voluntary modified directly observed therapy program in Rhode Island . Working in the context of a well-developed directly observed TB therapy program in Haiti, Farmer and colleagues have provided combination HIV antiretroviral therapy to 170 end-stage AIDS patients. In the absence of intensive laboratory monitoring, patients had excellent clinical responses to therapy and drug toxicity was rare. Individuals severely debilitated by the manifestations of end-stage AIDS have been able to return to work and care for their families .
While provocative, these initiatives do not demonstrate clear superiority of directly observed therapy to improve treatment outcomes. Retrospective chart review data reported by Hader suggests that directly observed HIV therapy in a residential treatment setting does not guarantee viral suppression in treatment-experienced patients . Notably, viral load differences seen in the Fischl study did not translate into a difference in CD4 cell counts, a more reliable predictor of clinical outcome. The program led by Farmer has demonstrated remarkable success. However, it is impossible to know how much of the effect is due to the merits of community driven and supportive healthcare, stable medication supply and distribution, the medication alone, or witnessed dosing.
Are resource-poor countries a ‘special case'?
Many believe that widespread poverty in resource-poor countries makes adherence a special concern for the provision of HIV therapy. USAID administrator Andrew Natsios has argued that Africans would be unable to adhere to antiretroviral regimens because they ‘don't know what Western time is,’ and ‘do not know what you are talking about,’ when asked to take drugs at specific intervals . However, early data suggest that adherence to combination antiretroviral therapy is at least as good as in resource-rich settings. Two recent South African studies found that adherence ranged from 88 to 95% in clinical trial settings that included impoverished participants [28,29]. In two separate studies with virologic outcomes, 65 and 92% of individuals living in South African townships maintained undetectable viral loads, better than in many clinic cohorts in wealthy countries [30–32].
These early recipients of antiretroviral therapy may not be representative of the larger HIV-positive population in resource-poor countries. Nonetheless, there is no evidence to suggest that adherence will be less in resource-poor countries. Studies with objective adherence measures indicate that HIV-positive individuals in wealthy countries take roughly 70% of their medication [33–38]. There is nothing to preclude equal or better adherence in resource-poor countries. The relatively uniform distribution of poverty in resource-poor settings is unlikely to concentrate mental illness and substance abuse to the degree found in resource rich settings and may therefore have different impacts on adherence.
The public health imperative to prevent the emergence of multi-drug resistant TB has generated much of the enthusiasm for directly observed TB therapy [39,40]. Drug resistant HIV is cited as an analogous concern. Early predictions that non-adherence to HIV therapy would lead to drug resistance, however, were based on a small number of patients either on protease inhibitor monotherapy or without well-characterized measures of adherence [41–44]. Recent findings argue for a revision of this view. In a cross-sectional study of adherence and resistance to protease inhibitor combination antiretroviral therapy, protease resistance mutations were seen only in patients with 65–100% adherence. Resistance to nucleoside reverse transcriptase inhibitors was also more common in highly adherent individuals . In separate reports, Walsh, Howard, Gallego, and Kuritzkes confirmed these findings [45–48]. These cross-sectional analyses have been confirmed with prospective analyses suggesting that the accumulation of new drug resistance mutations occurs most rapidly in patients with high levels of adherence but incomplete viral suppression, thus creating maximal drug pressure to select for and maintain resistant virus with impaired fitness . Because only one of two daily doses are observed during modified directly observed therapy, perfect adherence is not assured and once daily directly observed HIV therapy may place patients in an adherence window of 80–90% that maximally selects for drug resistant virus [50,51]. Improving adherence from levels too low to create drug resistance to levels optimal for drug resistance will likely improve short-term clinical outcomes, but will, nonetheless, compromise a key public health rationale for this approach [52,53].
Preventing HIV transmission
Observations by Quinn and colleagues indicate that the viral load is closely associated with the risk of HIV transmission in untreated serodiscordant heterosexual couples . Preventing HIV transmission is the strongest rationale for making adherence interventions a requirement of therapy. However, the assumption that treatment will prevent transmission and that treatment with directly observed therapy will prevent more transmission than treatment with self-administered therapy has not yet been tested. Even if this assumption is correct, we still must face the question of why calls for directly observed HIV therapy are limited to sub-Saharan Africa, and not North America or Western Europe.
Impact on individual rights
Hurtig and colleagues have discussed the negative impact of directly observed TB therapy programs on human rights . Because HIV is more stigmatizing than TB and requires lifelong therapy, the impact of similar HIV initiatives on confidentiality and liberty would be greater. Daily meetings with a health worker will disclose HIV infection to family, peers, and employers. In many countries hardest hit by HIV, the stigma of this disease is at least as powerful, if not more so, than in wealthy nations . Although the prospect of access to treatment may encourage individuals to determine their HIV status, the linkage of treatment to directly observed HIV therapy may paradoxically lower the use of counseling and testing services due to confidentiality concerns. In the USA, fears regarding HIV disclosure have led to a delay in treatment . These issues underscore the potential impact of compromising privacy by linking treatment to directly observed therapy programs.
Stigma is created and modified by social context. Both the Haitian and Rhode Island directly observed HIV therapy initiatives were designed to minimize stigma. In Haiti, ‘accompagnateurs’ deliver therapy to emphasize the partnership between the community health worker and patient rather than the act of witnessed dosing. Large scale directly observed HIV therapy programs across international boundaries will have more difficulty addressing societal factors that reinforce stigma. Thus, the Haiti and Providence examples may become the exception rather than the rule.
In the case of TB, compromised confidentiality and restrictions in movement have been deemed an acceptable social price to pay for effective disease control. These concerns are similar in kind, but greater in magnitude for HIV than for TB. If we are to allow a curtailment of individual rights among those seeking HIV treatment, we must demonstrate that powerful public health benefits will follow from this approach.
Balancing individual with population benefits
The appropriate role of directly observed HIV therapy will be decided largely by balancing the interests of individuals with those of populations. Directly observed HIV therapy may provide clinical benefit to some individuals. However, data to characterize this benefit are limited. The main attractions of directly observed HIV therapy are twofold. One is the perception that monitored medication dosing will prevent drug resistance. The other is that directly observed therapy may reduce transmission . Thus, the perceived population benefits, more than individual gains, drive support for directly observed HIV therapy. These population benefits are the clearest justification for limitations on individual freedom and threats to confidentiality imposed by directly observed therapy. Yet, it is these benefits that are most in question.
While we suggest restraint in the enthusiasm for directly observed HIV therapy as part of routine HIV care, we do not want to minimize the importance of developing effective and culturally appropriate voluntary adherence interventions to improve individual treatment outcomes globally. Adherence is both the greatest challenge and the single most important determinant of clinical outcome [59–61]. Optimal adherence strategies, including optional and voluntary directly observed HIV therapy, should be evaluated in several areas: virologic and immunologic outcomes, clinical outcomes, and transmission.
While the public health advantages of directly observed HIV therapy are in question, the impact on individual freedoms is not. We do not require direct observation of HIV therapy in resource-rich countries, and unless rigorous studies find important differences in adherence, there is no rationale for a different approach in resource-poor settings. Daily monitoring of adherence should either be optional and voluntary or confer an unequivocal public health benefit. The rationale for delivering HIV therapy to resource-poor countries is based on equity. We should not assume inequity with respect to people's ability to self-direct their medical care, including adherence to therapy.
Sponsorship: Supported by The Doris Duke Charitable Foundation and NIMH #54907h,63,011,66654. The Epidemiology and Prevention Interventions Center and The San Francisco General Hospital AIDS Program are components of the UCSF AIDS Research Institute.
1.UNAIDS. Report on the Global HIV/AIDS Epidemic.
Geneva: UNAIDS; 2000.
2.Harries AD, Nyangulu DS, Hargreaves NJ, Kaluwa O, Salaniponi FM. Preventing antiretroviral anarchy in sub-Saharan Africa. Lancet
3.Laurence J. The cost effectiveness of antiretroviral therapy for HIV disease. N Engl J Med
:68; discussion 68–69.
4.Little SJ, Routy P, Daar ES, Markowitz M, Collier AC, Kop RA, et al
. Antiretroviral drug susceptibility and response to initial therapy among recently HIV-infected subjects in North America. Eighth Conference on Retroviruses and Opportunistic Infections
. Chicago, February 2001 [abstract 756].
5.Popp D, Fisher JD. First, do no harm: a call for emphasizing adherence and HIV prevention interventions in active antiretroviral therapy programs in the developing world. AIDS
6.Harvard University. Consensus Statement on Antiretroviral Treatment for AIDS in Poor Countries.
Boston: Harvard University; 2001.
7.Farmer P, Learndre F, Mukherjee J, Gupta R, Tarter L, Kim J. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy). World Health Bull
8.Mbewu A. Antiretroviral therapy is only part of it. World Health Bull
9.United Nations. Blueprint for Action. Africa Recovery
10.James J. Malawi plan to control AIDS Epidemic: Interview with David Scondras. AIDS Treatment News
11.Salaniponi F. Using lessons learned in the control of tuberculosis to design a structured framework for providing antiretroviral therapy in Malawi. Adv Studies Med
12.Bayer R, Dubler NN, Landesman S. The dual epidemics of tuberculosis and AIDS: ethical and policy issues in screening and treatment. Am J Public Health
13.WHO. Treatment of Tuberculosis. Guidelines for National Programmes.
Geneva: WHO; 1997.
14.Zhang LX, Tu DH, Enarson DA. The impact of directly-observed treatment on the epidemiology of tuberculosis in Beijing. Int J Tuberc Lung Dis
15.Squire S, Wilkinson D. Strengthening DOTS through community care for tuberculosis. BMJ
16.Volmink J, Garner P. Systematic review of randomised controlled trials of strategies to promote adherence to tuberculosis treatment [see comments]. BMJ
17.Frieden TR, Fujiwara PI, Washko RM, Hamburg MA. Tuberculosis in New York City—turning the tide. N Engl J Med
18.Zwarenstein M, Schoeman JH, Vundule C, Lombard CJ, Tatley M. Randomised controlled trial of self-supervised and directly observed treatment of tuberculosis. Lancet
19.Kamolratanakul P, Sawert H, Lertmaharit S, Kasetjaroen Y, Akksilp S, Tulaporn C, et al
. Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand. Trans R Soc Trop Med Hyg
20.Walley JD, Khan MA, Newell JN, Khan MH. Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Lancet
21.Khan M, Walley J, Witter S, Imran A, Safdar N. Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Health Policy Plan
22.Volmink J, Matchaba P, Garner P. Directly observed therapy and treatment adherence. Lancet
23.Fischl M, Rodriguez A, Scerpella E, Mondroig R, Thompson L, Rechtine D. Impact of directly observed therapy on outcomes in HIV clinical trials. Seventh Conference on Retroviruses and Opportunistic Infections.
San Francisco, January 2000 [abstract 71].
24.Mitty JA, Stone VE, Sands M, Macalino G, Flanigan T. Directly observed therapy for the treatment of people with human immunodeficiency virus infection: a work in progress. Clin Infect Dis
25.Farmer P, Leandre F, Mukherjee JS, Claude M, Nevil P, Smith-Fawzi MC, et al
. Community-based approaches to HIV treatment in resource-poor settings. Lancet
26.Hader S, Weidle P, Cergnul I, Hanson D, Berkman A, Filmore H, et al
. Directly Observed Antiretroviral Therapy (DART) in Residential Treatment Facilities in New York City. Eighth Conference on Retroviruses and Opportunistic Infections
. Chicago, February 2001 [abstract 476].
27.Donnelly J. Prevention urged in AIDS fight; Natsiohs says funds should spend less on HIV treatment. Boston Globe
, June 7, 2001.
28.Orrell C, Bangsberg DR, Badri M, Wood R. Adherence is not a barrier to successful antiretroviral therapy treatment outcomes in south Africa.
2003, AIDS. 17
29.Laurent C, Diakhate N, Gueye NFN, Touré MA, Sow PS; Faye MA, et al
. The Senegalese government's highly active antiretroviral therapy initiative: an 18 month follow-up study. AIDS
30.Sanne I, Ive P, Mcintyre J, Gray G, Mohpapi L, Wood R. Successful antiretroviral therapy in clinical research in South Africa. First IAS Conference on HIV Pathogenesis and Treatment.
Buenos Aires, July 2001 [abstract 321].
31.Kasper T, Hilderbrand H, Tshabane N, et al
. Antiretroviral therapy in primary health care centers in a South African township. XIV International Conference on AIDS.
Barcelona, July 2002 [abstract MoOrB1095].
32.Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med
33.Paterson DL, Swindells S, Mohr J, Brester M, Squier C, Wagener MM, et al
. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med
34.McNabb J, Ross JW, Abriola K, Turley C, Nightingale CH, Nicolau DP. Adherence to highly active antiretroviral therapy predicts virologic outcome at an inner-city human immunodeficiency virus clinic. Clin Infect Dis
35.Arnsten JH, Demas PA, Farzadegan H, Grant RW, Gourevitch MN, Chang CJ, et al
. Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring. Clin Infect Dis
36.Liu H, Golin CE, Miller LG, Hays RD, Beck CK, Sanandaji S, et al
. A comparison study of multiple measures of adherence to HIV protease inhibitors. Ann Intern Med
37.Bangsberg DR, Hecht FM, Charlebois ED, Hays RD, Beck CK, Sanandaji S, et al
. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS
38.Gross R, Bilker WB, Friedman HM, Strom BL. Effect of adherence to newly initiated antiretroviral therapy on plasma viral load. AIDS
39.De Cock KM, Chaisson RE. Will DOTS do it? A reappraisal of tuberculosis control in countries with high rates of HIV infection. Int J Tuberc Lung Dis
40.Chaisson RE, Coberly JS, De Cock KM. DOTS and drug resistance: a silver lining to a darkening cloud. Int J Tuberc Lung Dis
41.Wainberg MA, Friedland G. Public health implications of antiretroviral therapy and HIV drug resistance [see comments]. JAMA
42.Altice FL, Friedland GH. The era of adherence to HIV therapy [editorial]. Ann Intern Med
43.Vanhove GF, Schapiro JM, Winters MA, Merigan TC, Blaschke TF. Patient compliance and drug failure in protease inhibitor monotherapy [letter]. JAMA
44.Montaner JS, Reiss P, Cooper D, Vella S, Harris M, Conway B; Wainberg MA, et al
. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study [see comments]. JAMA
45.Walsh JC, Pozniak AL, Nelson MR, Mandalia S, Gazzard BG. Virologic rebound on HAART in the context of low treatment adherence is associated with a low prevalence of antiretroviral drug resistance. J Acquir Immune Defic Syndr
46.Howard A, Arnsten J, Gardner L, et al
. Lack of multi-drug resistance in nonresponders to antiretroviral therapy with poor adherence. First IAS Conference on HIV Pathogenesis and Treatment.
Buenos Aires, July 2001 [abstract 604].
47.Gallego O, de Mendoza C, Perez-Elias MJ, Guardiola JM, Pedreira J, Dalmau D, et al
. Drug resistance in patients experiencing early virological failure under a triple combination including indinavir. AIDS
48.Kuritzkes D, Ickovics J, Bassett R, Hellman N, Johnson V. HIV-1 drug resistance and medication adherence in patients receiving NRTIs. HIV Resistance and Pathogenesis Meeting
. Scottsdale, June 2001. [abstract 84]
49.Bangsberg D, Charlebois E, Grant R, Holodniy M, Perry S, Nugent Conroy K, et al
. Low levels of adherence do not increase risk of HIV drug resistance. Ninth Conference on Retroviruses and Opportunistic Infections
. Seattle, AIDS
, in press.
50.Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, et al
. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med
51.Stenzel M, McKenzie M, Adelson-Mitty J, Flanigan T. Modified directly observed therapy (MDOT) to enhance adherence to highly active antiretroviral therapy (HAART): 12 month follow-up. XIII International Conference on AIDS.
Durban, July 2000 [abstract ThPeb4992].
52.Bangsberg DR, Kagay CR, Porco T, Grant R, Holodniy M, Charlebois ED, et al
. Modeling the relationship between adherence and accumulation of protease inhibitor drug resistance mutations based on objectively measured adherence and empirically derived relationships. XIth HIV Drug Resistance Workshop.
Seville July 2002 [abstract 160].
53.Kagay C, Porco T, Moss AR, Bangsberg DR. Modified directly observed therapy and adherence case managment improve HIV clinical outcomes but fail to prevent drug resistance. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy.
San Diego, September 2002.
54.Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, et al
. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group [see comments]. N Engl J Med
55.Hurtig AK, Porter JD, Ogden JA. Tuberculosis control and directly observed therapy from the public health/human rights perspective. Int J Tuberc Lung Dis
56.Enzama R, Mbuga F, Turyatemba C. Strategies for delivery of ARVs. First IAS Conference on HIV Pathogenesis and Treatment.
Buenos Aires, July, 2001 [abstract 327].
57.Whetten-Goldstein K, Nguyen TQ, Sugarman J. So much for keeping secrets: the importance of considering patients’ perspectives on maintaining confidentiality. AIDS Care
58.Fiscus S, Cohen M. Impact of antiretroviral therapy on the transmission of HIV. National HIV Prevention Conference
. Atlanta August, 2001.
59.Hogg RS, Heath K, Bangsberg D, Yip B, Press N, O'Shaughnessy MV, et al
. Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. AIDS
60.Bangsberg DR, Perry S, Charlebois ED, Clark RA, Roberston M, Zolopa AR, et al
. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS
61.deOlalla P, Knobel H, Carmona A, Guelar A, Lopez-Colomes J, Cayla J. Impact of adherence on highly active antiretroviral therapy on survival in HIV-infected patients. J Acquir Immune Def Syndr
This article has been cited 30 time(s).
M S-Medecine Sciences
HIV drug resistance and optimization of antiviral treatment in resource-poor countries
M S-Medecine Sciences, 20():
American Journal of Public HealthUnderstanding and addressing AIDS-related stigma: From anthropological theory to clinical practice in HaitiAmerican Journal of Public Health
Jama-Journal of the American Medical Association
Adherence to antiretroviral therapy in sub-Saharan Africa and North America - A meta-analysis
Jama-Journal of the American Medical Association, 296(6):
LancetDirectly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trialsLancet
American Journal of Public HealthAntiretroviral therapy in resource-poor countries: Illusions and realitiesAmerican Journal of Public Health
AIDS Patient Care and Stds
Multidisciplinary, inpatient directly observed therapy for HIV-1-infected children and adolescents failing HAART: A retrospective study
AIDS Patient Care and Stds, 20(4):
Clinical Infectious Diseases
Lessons learned from use of highly active antiretroviral therapy in Africa
Clinical Infectious Diseases, 41(3):
AIDS and BehaviorCommunity-based DOT-HAART Accompaniment in an Urban Resource-Poor SettingAIDS and Behavior
Revista Panamericana De Salud Publica-Pan American Journal of Public Health
Assessing HIV resistance in developing countries: Brazil as a case study
Revista Panamericana De Salud Publica-Pan American Journal of Public Health, 19(3):
Chinese Medical JournalImproving China's antiretroviral treatment program: assessing current and future performance using the principals of ethicsChinese Medical Journal
AIDS'DOTS' and 'DOT' for delivering antiretroviral therapy in resource-poor countriesAIDS
Revue D Epidemiologie Et De Sante Publique
Directly observed therapy (DOT): from tuberculosis to HIV
Revue D Epidemiologie Et De Sante Publique, 54(1):
Plos MedicineAdherence to HAART: A systematic review of developed and developing nation patient-reported barriers and facilitatorsPlos Medicine
Ajar-African Journal of AIDS ResearchAdherence to antiretroviral therapy among HIV-infected children attending a donor-funded clinic at a tertiary hospital in NigeriaAjar-African Journal of AIDS Research
Medecine Et Maladies InfectieusesObservance of antiretroviral treatments: African specificitiesMedecine Et Maladies Infectieuses
Jaids-Journal of Acquired Immune Deficiency Syndromes
Modified directly observed therapy to facilitate highly active antiretroviral therapy adherence in Beira, Mozambique - Development and implementation
Jaids-Journal of Acquired Immune Deficiency Syndromes, 43():
International Journal of Tuberculosis and Lung Disease
Highly active antiretroviral therapy (HAART) in adults with tuberculosis: current status
International Journal of Tuberculosis and Lung Disease, 9(3):
Clinical Infectious Diseases
Modeling the impact of modified directly observed antiretroviral therapy on HIV suppression and resistance, disease progression, and death
Clinical Infectious Diseases, 38():
British Medical Journal
Expanding antiretroviral therapy in Malawi: drawing on the country's experience with tuberculosis
British Medical Journal, 329():
AIDS and BehaviorThe price of adherence: Qualitative findings from HIV positive individuals purchasing fixed-dose combination generic HIV antiretroviral therapy in Kampala, UgandaAIDS and Behavior
Disease Management & Health Outcomes
Efficiency of interventions in HIV infection, 1994-2004
Disease Management & Health Outcomes, 13(6):
AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HivHIV/AIDS in fishing communities: Challenges to delivering antiretroviral therapy to vulnerable groupsAIDS Care-Psychological and Socio-Medical Aspects of AIDS/Hiv
Clinical Infectious DiseasesSuperiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: A prospective, randomized, controlled trialClinical Infectious Diseases
Ajar-African Journal of AIDS ResearchDisclosure of HIV status: experiences of patients enrolled in an integrated TB and HAART pilot programme in South AfricaAjar-African Journal of AIDS Research
AIDSDrug resistance and adherence to HIV/AIDS antiretroviral treatment: against a double standard between the north and the southAIDS
JAIDS Journal of Acquired Immune Deficiency SyndromesHome-Based Antiretroviral Care Is Associated With Positive Social Outcomes in a Prospective Cohort in UgandaJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesPriorities for Antiretroviral Therapy Research in Sub-Saharan Africa: A 2002 Consensus Conference in ZambiaJAIDS Journal of Acquired Immune Deficiency Syndromes
HIV antiretroviral therapy; Africa; resource-poor; adherence; resistance; directly observed therapy
© 2003 Lippincott Williams & Wilkins, Inc.
Highlight selected keywords in the article text.