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Antiretroviral Therapy in Resource-Poor Settings Decreasing Barriers to Access and Promoting Adherence Joia S. Mukherjee, MD, MPH,* Louise Ivers, MD, MPH, DTMH,* Fernet Leandre, MD,† Paul Farmer, MD, PhD,* and Heidi Behforouz, MD* access to the clinic and the medications. Because some of the Summary: Since 2002, the HIV Equity Initiative of the non- risk factors for nonadherence described in North American governmental organization Partners in Health has been expanded in studies, such as active drug use, are more common in poor conjunction with the Haitian MOH to cover 7 public clinics. More populations,5 when ART was introduced in resource-poor set- than 8000 HIV-positive persons, 2300 of whom are on antiretroviral tings, there was fear that adherence would be a major problem therapy (ART) are now followed. This article describes the and promote widespread resistance to ART.6,7 However, interventions to promote access to care and adherence to ART studies in developing countries have shown comparable or developed in reference to the specific context of poverty in rural Haiti.
better levels of individual adherence than what is seen in North User fees for clinic attendance have been waived for all patients with American and European populations.8,9 Resource-limited HIV and tuberculosis and for women presenting for prenatal services.
settings, however, present unique challenges to ART adher- Additionally, HIV testing has been integrated into the provision of ence. A multitude of structural barriers prevent access to health primary care services to increase HIV case finding among those care and the regular supply of antiretroviral drugs. These presenting to clinic because of illness, rather than solely focusing on include the cost of medical care, drugs, lack of integration of those who present for voluntary counseling and testing (VCT). Once HIV testing with primary health care, tuberculosis, STI and a patient is diagnosed with HIV, medications and monitoring tests are women’s health services, and the difficulty on making provided free of charge and transportation costs for follow-up follow-up appointments during the long distances, family appointments are covered to defray patients’ out-of-pocket expenses.
responsibilities, and the prohibitive cost of transportation.
Patients are given home-based adherence support from a network of These factors affect the patient’s ability to take medications as health workers who provide psychosocial support and directly prescribed by the health care provider.
observed therapy. In addition, the neediest patients receive nutritional This article discusses the interplay between access and support. Following the description of the program is an approxima- adherence in resource-poor settings and, based on our work tion of the costs of these interventions and a discussion of their in rural Haiti with poor communities, outlines strategies to decrease barriers to access and to increase adherence to ART.
Finally, based on our experience, we estimate the costs of Key Words: adherence, antiretroviral therapy, community health implementing these access and adherence support strategies in workers, nutrition, resource-poor settings, user fees (J Acquir Immune Defic Syndr 2006;43:S123–S126) Adherence to antiretroviral therapy (ART) delays the Since 1998, the nongovernmental organization (NGO) progression to AIDS1,2 and the development of antire- Partners in Health (PIH) has been providing ART to people troviral resistance.3 Much of the medical literature on through a charity hospital, the Clinique Bon Sauveur, in Haiti’s adherence to ART is focused on measuring the individual Central Department under the HIV Equity Initiative (HEI). In patient’s ability to take ART as prescribed.4 The underlying 2002, the initiative was expanded into the public clinics in assumption in much of this body of work is that once the collaboration with the Haitian Ministry of Health (MSPP) and medicines are prescribed, the patient has regular and reliable now covers 7 public clinics, following more than 8000 HIV-positive persons, 2300 of whom are on ART. Most of thepeople served by the clinics are poor subsistence farmers or From the *Division of Social Medicine and Health Inequalities, Brigham and have been migrant workers in urban Port-au-Prince or the Women’s Hospital, Harvard Medical School, Boston, MA; and Zanmi plantations of the Dominican Republic. The prevalence of HIV is 5% among people attending the general clinics and 2% Supported by Frank Hatch Fellowships (J. S. Mukherjee and H. Behforouz), Partners In Health (F. Leandre), the Clinton Foundation (F. Leandre), the among pregnant women. The lessons learned from the early Eli Lilly Foundation (J. S. Mukherjee), and the National Institutes of phase of the HEI was that the context of poverty factors such as Health (L. Ivers, H. Behforouz, and J. S. Mukherjee).
lack of access to transport, food insecurity, and user fees for Reprints: Joia Mukherjee, MD, MPH, Division of Social Medicine and Health medical care, posed more significant barriers to adhering to Inequalities, Brigham and Women’s Hospital, Harvard Medical School, 641 long-term therapy than a patient’s individual behavior. Several Huntington Avenue, Boston, MA 02115 (e-mail: jmukherjee@pih.org).
Copyright Ó 2006 by Lippincott Williams & Wilkins critical components were put into place to decrease these J Acquir Immune Defic Syndr  Volume 43, Supplement 1, December 1, 2006 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Acquir Immune Defic Syndr  Volume 43, Supplement 1, December 1, 2006 barriers. First, all services and medications are provided free ofcharge to the patient. It has been documented by severalprojects that user fees are a significant barrier to seeking HIVtesting, obtaining laboratory evaluations, and attendingfollow-up appointments.10 Such cost sharing is detrimentalto long-term adherence, as data from Senegal11 and Botswana9indicate. In the HEI, user fees for services (visits andmonitoring) and all medications are waived entirely. Alltreatment is given free of charge (including not only ART butdrugs for opportunistic infections, family planning, andmedications for other conditions such as hypertension).
Second, HIV testing, treatment, and care are provided in the context of primary care services. This is particularlyimportant and primary care clinics were revitalized byproviding essential medicines and paying stipends to MSPP FIGURE 1. VCT uptake with introduction of HIV–primary health staff in rural areas where patients routinely walk 4 or more care integration: Lascahobas versus Cange. (From Walton D, hours to seek care. Most of the people attending the Farmer P, Lambert W, et al. Integrated HIV prevention and care PIH/MSPP clinics come only when they are ill rather than strengthens primary health care: lessons from rural Haiti.
to seek testing for HIV per se. In the context of primary health J Public Health Policy. 2004;25:137–158; with permission.) care, ill patients are screened for tuberculosis, treatable causesof diarrheal disease, sexually transmitted diseases, and otherconditions that may be associated with HIV. As part of the therapy to HIV patients requiring ART. The development and evaluation of the ill patient, HIV testing may be offered by the activities of these workers have been described in detail clinician, if indicated. This strategy, sometimes called ‘‘opt out’’ or ‘‘routine offer’’ HIV testing, has been found to beacceptable in many settings, particularly when ART isavailable.12,13 The third aspect of the program to increase access and The Zamni Lasante proposal written to the Global Fund adherence to HIV treatment is an attempt to minimize the to Fight AIDS, Tuberculosis, and Malaria and, later, the significant out-of-pocket expenses. Studies from several President’s Emergency Plan for AIDS Relief included the settings have shown that costs such as payment for trans- staffing and essential medications that would be needed to portation to and from a clinic serve as a deterrent to ART increase the provision of primary health services that would be adherence. Patients attending PIH/MSPP clinic receive expected for the population at each site. The improvement in a monthly transportation stipend to attend follow-up appoint- general health services, done with money for HIV scale-up, ments. Transportation for emergency visits is also covered by served to markedly increase the utilization of primary health the program.14 Similarly, a lack of food has been associated with care. With this context, we presumed the uptake of HIV testing poor adherence to ART, and provision of food and micro- nutrients has been shown to improve outcomes15–17 Many To discern whether or not the packages of interventions families throughout the developing world spend more than 50% described previously (discontinuing user fees, integrating HIV of their household income on food, and food production and testing with primary health care, and providing transport fees wage earning are adversely affected when an adult has and other material assistance to patients) increased the overall AIDS.18,19 Therefore, the PIH/MSPP program provides food uptake of HIV testing and the use of health care services, or cash transfers for food to the most vulnerable patients.
records were analyzed from the Lascahobas MSPP clinic from The fourth aspect of the HEI program to support adher- the beginning of the integrated PIH/MSPP program in October ence and minimize barriers to access is the use of community 2002 through the end of 2003. The results of that analysis, health workers. Community health workers perform active which have been published elsewhere,22 are seen in Figure 1.
case finding for HIV and tuberculosis and provide a link The number of VCT sessions at Lascahobas increased between the patient, family, community, and clinic. Their daily dramatically after initiation of the program and compares role is to give psychologic support and directly observed favorably with the rates reported from the referral center in TABLE 1. Use of Services After the HIV–Primary Health Care Integrated Model of Care Was Implemented MSPP–Zanmi Lasante Community Partnership Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Acquir Immune Defic Syndr  Volume 43, Supplement 1, December 1, 2006 Antiretroviral Therapy in Resource-Poor Settings TABLE 2. Approximate Costs of Adherence and Access Interventions in the PIH/MSPP HEI Monthly visits to clinic, normal user fee $0.05 per month 3 12 months Yearly CD4 cell count, radiographs, hemoglobin, liver function tests Transportation fees for monthly clinic visit Monthly transport fee $5 per month 3 12 months Community health worker paid $500 per year for coverage of 5 patients Cange Clinique, Bon Sauveur, where HIV VCT and full a delay in the need for second-line ART. Second-line primary health care services have been available since 1986.
antiretroviral medications, typically lopinivir/ritonovir, teno- With this series of interventions, 40,000 HIV tests were fovir, and abacavir, are not available as generic drugs and cost performed in 2005. 2300 patients are on ART. Of the 1500 approximately $1500 US per patient per year. Thus, each year patients who have been on ART for more than 1 year, fewer the need for a second-line regimen is delayed, $13,000 US is than 100 have died or had clinical or immunologic failure that saved in antiretroviral costs. Additionally, patients are more required a change to second-line ART, suggesting excellent likely to remain healthy and out of the hospital if resistance is adherence to ART and medical follow-up. Virologic monitor- ing has not yet been performed in this population because of In the United States, where adherence support is not universal, approximately 50% of patients on a new anti- Although there are many facets to the HEI adherence retroviral regimen develop a detectable viral load (the precursor and access interventions, some of the costs can be estimated.
of resistance) at the end of 1 year,23 but little has been done to Table 2 outlines the cost of the various interventions. The provide financial support for adherence programs.
transportation fee averages $60 US per patient per year. The The challenge of administering long-term therapy in set- cost of waiving the MSPP user fee for 12 monthly visits is $6 tings of extreme privation is significant. Although adherence US per patient per year. The cost of waiving the cost for to ART is much discussed in the public health arena, little has ancillary tests (including a yearly CD4 cell count, radiographs, been done to advocate for financial support of initiatives that and routine laboratory monitoring tests) is approximately $20 have been shown to improve adherence. HIV program should US per year. This standard package adds up to approximately be rooted in sole primary health care to benefit a greater $86 US per year per patient. Community health workers are proportion of the community. HIV diagnosis, treatment, and paid approximately $500 US per year and follow, on average, 5 monitoring should be provided free of charge in poor patients, adding a cost of $100 US per patient per year. The communities to ensure that drugs are taken properly and not total cost of the adherence package is $186 US per year.
shared with family members or sold. Additionally, with the Patients who have severe wasting and children with HIV millions of dollars being invested in the scale-up of ART, who have signs of malnutrition receive nutritional support. We a lack of food security in the most heavily HIV-burdened estimate that the cost of food for the patients who are countries threatens HIV programs and the health and survival economically and nutritionally the neediest is approximately $450 US per year. This intervention is currently beingevaluated in partnership with the World Food Program.
1. de Olalla PG, Knobel H, Carmona A, et al. Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients.
Scale-up of HIV testing and treatment cannot be done J Acquir Immune Defic Syndr. 2002;30:105–110.
2. Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly without improving access to primary health care and active antiretroviral therapy predicts progression to AIDS. AIDS. 2001;15: integrating HIV services with that context. Moreover, adherence programs in resource-poor settings must work to 3. Bangsberg D, Hecht F, Charlebois E, et al. Adherence to protease inhibitors, HIV-1 viral load and development of drug resistance in an The low rate of treatment failure, indicated by few indigent population. AIDS. 2000;14:357–366.
4. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy deaths and few patients needing to change to second-line ART, in a large urban clinic: risk factors for virologic failure and adverse drug suggests that adherence to medical follow-up and antiretroviral reactions. Ann Intern Med. 1999;131:81–87.
medication is excellent in the HEI. Monitoring of virologic 5. Steiner JF, Prochazka AV. The assessment of refill compliance using response and for the development of resistance within the pharmacy records: methods, validity and applications. J Clin Epi. 1997;50:105–116.
cohort of patients on ART is planned for this year. Additional 6. Harries AD, Nyangulu DS, Hargreaves NJ, et al. Preventing antiretroviral work is planned to focus on measuring the impact and cost of anarchy in Africa. Lancet. 2001;358:410–414.
individual interventions on clinic attendance and adherence. A 7. Frater AJ, Dunn DT, Beardall AJ, et al. Comparative response of African first-line nevirapine-based generic antiretroviral regimen costs HIV-1 infected individuals to highly active antiretroviral therapy. AIDS.
approximately $150 US per person per year. Our basic 8. Orrell C, Bangsberg DR, Badri M, et al. Adherence is not a barrier package of support costs approximately $186 US. Investments to successful antiretroviral therapy in South Africa. AIDS. 2003;17: in adherence, if effective, should yield a return in the form of Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Acquir Immune Defic Syndr  Volume 43, Supplement 1, December 1, 2006 9. Weiser S, Wolfe W, Bangsberg D, et al. Barriers to antiretroviral adherence in HIV-infected women from Tanzania. Am J Clin Nutr. 2005;82: for patients living with HIV infection and AIDS in Botswana. J Acquir Immune Defic Syndr. 2003;34:281–288.
17. Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of 10. Russell S. The economic burden of illness for households in development multivitamin supplements and HIV disease progression and mortality. N countries: a review of the studies focusing on malaria, tuberculosis and HIV/AIDS. Am J Trop Med Hyg. 2004;71(Suppl 2):147–155.
18. Rutengwe RM. Identifying strategic interventions for improving 11. Laniece I, Ciss M, Desclaux A, et al. Adherence to HAART and its principal determinants in a cohort of Senegalese adults. AIDS. 2003;17 settlement, South Africa. Asia Pac J Clin Nutr. 2004;13(Suppl): 12. Centers for Disease Control. Introduction of routine HIV testing in 19. Smith Fawzi MC, Lambert W, Singler JM, et al. Factors associated with prenatal care—Botswana, 2004. MMWR Morb Mort Wkly Rpt. 2004;53: forced sex among women in rural Haiti: implications for the prevention of HIV and other STDs. Soc Sci Med. 2005;60:679–689.
13. Westheimer EF, Urassa W, Msamanga G, et al. Acceptance of HIV testing Le´andre F, Mukherjee JS, et al. Community-based among pregnant women in Dar-es-Salaam, Tanzania. J Acquir Immune approaches to HIV treatment in resource-poor settings. Lancet. 2001; 14. Rowe KA, Makhubele B, Hargreaves JR, et al. Adherence to TB 21. Farmer P, Le´andre F, Mukherjee JS, et al. Community-based approaches to preventive therapy for HIV-positive patients in rural South Africa: the treatment of advanced HIV disease, introducing DOT-HAART. Bull implications for antiretroviral delivery in resource-poor settings? Int J World Health Organ. 2001;79:1145–1151.
22. Walton D, Farmer P, Lambert W, et al. Integrated HIV prevention and care 15. Ndekha MJ, Manary MJ, Ashorn P, et al. Home-based therapy with ready- strengthens primary health care: lessons from rural Haiti. J Public Health to-use therapeutic food is of benefit to malnourished, HIV-infected Malawian children. Acta Paediatr. 2005;94:222–225.
23. Gross R, Bilker WB, Friedman HM, et al. Effect of adherence to newly 16. Villamor E, Saathoff E, Manji K, et al. Vitamin supplements, initiated antiretroviral therapy on plasma viral load. AIDS. 2001;15: socioeconomic status, and morbidity events as predictors of wasting Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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