JAIDS Journal of Acquired Immune Deficiency Syndromes:
Implementation and Operational Research: Clinical Science
Excellent Clinical Outcomes and High Retention in Care Among Adults in a Community-Based HIV Treatment Program in Rural Rwanda
Rich, Michael L. MD, MPH*,†,‡; Miller, Ann C. PhD, MPH§; Niyigena, Peter RN‡; Franke, Molly F. ScD†,‡,§; Niyonzima, Jean Bosco MD‡; Socci, Adrienne MD†,‡; Drobac, Peter C. MD, MPH*,†,‡; Hakizamungu, Massudi MBA‡; Mayfield, Alishya MD‡; Ruhayisha, Robert MD‖; Epino, Henry MD†,‡,¶; Stulac, Sara MD*,†,‡; Cancedda, Corrado MD*,†,‡; Karamaga, Adolph MD‖; Niyonzima, Saleh MD‖; Yarbrough, Chase BA‡; Fleming, Julia BA‡; Amoroso, Cheryl MPH†,‡; Mukherjee, Joia MD, MPH*,†,§; Murray, Megan MD, ScD*,#; Farmer, Paul MD, PhD*,†,‡,§; Binagwaho, Agnes MD, PhD§,‖
*Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA
†Partners In Health, Boston, MA
‡Partners In Health/Inshuti Mu Buzima, Rwinkwavu, Rwanda
§Department of Global Health and Social Medicine, Harvard School of Medicine, Boston MA
‖Rwanda Ministry of Health, Kigali, Rwanda
¶Division of Emergency Medicine, Massachusetts General Hospital, Boston, MA
#Department of Epidemiology, Harvard School of Public Health, Boston, MA
Correspondence to: Ann C. Miller, PhD, MPH, Department of Global Health and Social Medicine, Harvard Medical School, 641 Huntington Avenue, Boston, MA 02115 (e-mail: email@example.com).
Supported by funding from Partners In Health, a 501(c)(3) charity.
Partners In Health staff performed data collection and contributed to article writing but were not involved in the analysis of the article. No other funders were involved in the research.
The authors have no conflicts of interest to disclose.
Received July 28, 2011
Accepted November 30, 2011
Background: Access to antiretroviral therapy (ART) has rapidly expanded; as of the end of 2010, an estimated 6.6 million people are receiving ART in low-income and middle-income countries. Few reports have focused on the experiences of rural health centers or the use of community health workers. We report clinical and programatic outcomes at 24 months for a cohort of patients enrolled in a community-based ART program in southeastern Rwanda under collaboration between Partners In Health and the Rwandan Ministry of Health.
Methods and Findings: A retrospective medical record review was performed for a cohort of 1041 HIV+ adult patients initiating community-based ART between June 1, 2005, and April 30, 2006. Key programatic elements included free ART with direct observation by community health worker, tuberculosis screening and treatment, nutritional support, a transportation allowance, and social support. Among 1041 patients who initiated community-based ART, 961 (92.3%) were retained in care, 52 (5%) died and 28 (2.7%) were lost to follow-up. Median CD4 T-cell count increase was 336 cells per microliter [interquartile range: (IQR): 212–493] from median 190 cells per microliter (IQR: 116–270) at initiation.
Conclusions: A program of intensive community-based treatment support for ART in rural Rwanda had excellent outcomes in 24-month retention in care. Having committed to improving access to HIV treatment in sub-Saharan Africa, the international community, including country HIV programs, should set high programmatic outcome benchmarks.
Access to antiretroviral therapy (ART) has rapidly expanded on a massive scale with more than 6.6 million people receiving ART in low-income and middle-income countries by end of 2010 and an estimated 3.7 million life-years saved in sub-Saharan Africa.1 Literature reviews of HIV programs in Africa and other resource-limited areas reveal notable variation in outcomes of mortality, default, and viral load suppression.2–10 Reports of effective strategies, and those that are less effective, inform program design and resource allocation; however, few reports have focused on the experiences of rural health centers with the use of community health workers (CHWs).
We describe outcomes from a community-based ART program that was implemented in rural Rwanda in June 2005. This program operated within the Rwanda national HIV care and treatment system, but provided additional measures of support at the community level, including community-based psychosocial support and directly observed ART delivered by CHWs, ongoing HIV education, nutritional assistance for 10 months, a travel allowance for routine visits, and comprehensive integrated medical care including diagnosis and treatment of one of the most important opportunistic infections, tuberculosis (TB). The program was a collaboration between the Rwanda Ministry of Health (MoH), the Global Fund for AIDS, Tuberculosis, and Malaria (GFATM), the Clinton Health Access Initiative and Partners In Health (PIH). PIH, a nongovernmental organization, currently provides ART to more than 13,000 patients in 11 different health system strengthening projects worldwide, utilizing more than 10,000 CHWs to help deliver care.11
Rwanda is the most densely populated country in Africa, with about 85% of the population engaged in subsistence agriculture and a per capita income of US $866.12 Life expectancy is 49.7 years, and the fertility rate remains high at 5.5 births per women.13 An estimated 169,000 adults in Rwanda (approximately 3%) are HIV positive. The Rwanda national ART program was established in 2004; by November 2009, more than 70,000 persons had begun treatment at 252 sites.14,15 During the study period, national guidelines indicated ART for individuals who met one of the following criteria: (1) WHO HIV stage 4; (2) WHO HIV stage 3 with a CD4 cell count <350 cells; (3) WHO stage 1 or 2 with a CD4 cell count <200 cells.16 This study represents the outcomes of 6 ART sites located in rural eastern Rwanda, covering a population of 410,000 persons.
The study population consisted of HIV-positive adults starting community-based ART treatment between June 1, 2005, and April 30, 2006. The primary outcome was retention in care 24 months after the community-based ART start date. Specifically, retention in care was defined as the presence of a documented clinic visit ±60 days of the 24-month anniversary date or a documented clinic visit in 7 of 8 calendar quarters after treatment initiation. Treatment initiation date was considered the documented date the patient began community-based treatment. For those with no documented clinic visit surrounding the 24-month ART anniversary, CHW visit record data was used to confirm whether the patient was retained in care. “Baseline” CD4 counts and weights were defined as the value with the recorded date closest to the ART start date (up to 60 days prior or 1 month post ART start date, if no prior data were collected.) “1 year” and “2 year” CD4 counts were defined as the values recorded closest to the anniversary date (±42 days). Patients who transferred to another ART facility were considered retained if there was a documented transfer sheet to a Rwanda MoH-approved ART treatment site. Individuals who left the program but returned after administrative closure (June 29, 2008—60 days after the last possible 24-month anniversary) were not considered retained. Individuals who were not retained (eg, died, defaulted, or were lost to follow-up) were defined as having experienced attrition from care.
The initial ART regimen was defined as the regimen that the patient initiated at the time of program enrollment, and the final regimen was defined as the regimen received at the time of the 24-month anniversary or the date of attrition from care.
Design of the ART Program
The program included all elements recommended by Rwanda national care and treatment guidelines,16 including free care and treatment to all HIV-infected persons, and a first-line triple drug ART regimen consisting of 2 nucleoside reverse transcriptase inhibitors plus 1 nonnucleoside reverse transcriptase inhibitor. Consistent with national protocols, CD4 counts were assessed every 6 months using a BD fluorescence-activated cell sorting Count system (Becton Dickinson TM, La Pont de Claix, France). Cotrimoxazole (or dapsone for those with cotrimoxazole intolerance) was prescribed to all patients with CD4 of <350 cells per microliter. Scheduled follow-up visits and unscheduled visits were free of charge for all patients in the program, and all patients were screened for TB and treated if diagnosed with active TB disease. Although this community-based ART program operated within the national system, it incorporated a number of enhancements designed to address social and economic barriers to adherence and retention. Box 1 contains detailed descriptions of these enhancements.
BOX 1 Additional Components of the Community-Based ART Program Cited Here...
Data Collection and Analysis
Data were abstracted from paper charts at the ambulatory clinics, double entered into a database, reconciled, combined with data from an electronic medical record based on Open Medical Record System (OpenMRS Inc., Indianapolis, IN) and analyzed using Stata SE/10.0 (College Station, TX). For a subset of the first 275 patients to complete 24 months of ART, plasma HIV viral load testing (Roche Molecular Systems, Meylan, France) was performed.
Analysis of factors associated with retention in care was conducted using logistic regression. Factors that were statistically significant predictors of retention at a P value <0.25 in unadjusted analysis were considered for inclusion into the final multivariable model.17 Data were evaluated for interactions between all significant variables. A model with all variables and interactions significant at P <0.25 was fit, and separate models dropping a single individual component were tested against the full model using likelihood ratio testing to produce the final model. Rather than building treatment site into the model, we used this as a clustering variable in the final model. Due to limited resources available for viral load testing, efforts were concentrated to obtain viral load on the first 300 enrolled patients with 24 months in the program, of which 275 tests (92%) were completed and reported.
The study was reviewed and approved by the Rwanda National Ethics Committee in Kigali, Rwanda, and the Institutional Review Board at Brigham and Women's Hospital in Boston, MA.
The study cohort comprised 1041 patients. Baseline characteristics are shown in Table 1. The mean age at enrollment was 38 years (range: 15–75). Median baseline CD4 T-cell count for the cohort was 190 cells per microliter [Interquartile range (IQR): 116–270]. Almost all patients were enrolled with an initial CD4 count of <350 cells per microliter (96.2%) and more than half had a baseline CD4 count of <200 cells per microliter (52.7%).
Program Outcomes at 2 Years and Predictors of Retention After Treatment Initiation
Two years after community-based ART initiation, 961 patients (92.3%) were retained in care, 52 (5%) had died, and 28 (2.7%) were lost to follow-up or had defaulted (Fig. 1). Of the 961 individuals retained in care, 35 (3.4% of the initial cohort) were transferred to other HIV treatment programs within Rwanda. Of the 52 patients known to have died, death dates were available for 45. Thirty-five (78%) died in the first 12 months of ART and 10 (22%) died between their first and second anniversary. For the remaining 7, all had a last visit before their first anniversary.
The factors associated with attrition from care are shown in Table 2. In unadjusted analysis, we found that patients were less likely to be retained in care if they were male [odds ratio (OR): 2.11 (1.33, 3.33)], were >50 years of age at treatment initiation [OR: 3.02 (1.73, 5.29)], had a WHO HIV stage of 3 or 4 at baseline [OR: 2.29 (1.22, 4.31)], or had a baseline CD4 count of less than 200 [OR: 1.32 (1.03, 1.70)]. The final multivariable regression model adjusted for WHO stage at baseline (stage 1 or 2 vs. stage 3 or 4), baseline CD4 T-cell count (<200 or ≥200 cells/uL), gender, year of ART initiation (June to December 2005 vs. January to May 2006), >50 years of age at treatment initiation, and an interaction term for sex and WHO stage. In multivariable analysis, age older than 50 years [OR: 2.48 (1.31, 4.71)] and enrollment in 2006 [OR: 1.85 (1.25, 2.73)] were associated with attrition. An interaction existed between WHO stage at baseline and sex. Among women, WHO clinical stage was not significantly associated with retention in care. However, attrition was significantly less likely among men with WHO stages 1 or 2 [OR: 0.21 (0.06, 0.80)], and more likely in men with WHO stage 3 or 4 disease at baseline [OR: 3.16 (1.42, 7.04)].
Of the 275 with testing at their 2-year anniversary, 232 (84.4%) had <40 copies per milliliter and 268 (97.5%) had <500 copies/ per milliliter (Table 3). Characteristics of patients who did and did not receive viral load testing are shown in Table 1. Those who received viral load testing were among the first to initiate ART in this program and on average had more advanced HIV disease, with a higher likelihood of WHO stage 4 disease at baseline (8.0% vs. 3.7%), and median CD4 counts that were 20 points lower (174 vs. 196) relative to those who did not undergo viral load testing.
Two-year CD4 T-cell counts were available for 710 patients; median increase in CD4 T-cell count was 336 cells per microliter (IQR: 212–493). Of the 356 patients who started treatment with CD4 counts <200 cells per microliter, the median increase was 323.5 cells per microliter (IQR: 204.5–474.5).
After 1 year of ART, median weight increase from baseline among 787 patients for whom data were available was 3.5 kg (IQR: 1–7). At year 2, median weight increase from baseline among 774 patients for whom data were available was 2 kg (IQR: −1 to 7).
Regimen data were available for 1040 (99.9%) of the 1041 patients. Table 4 lists the initial regimens used and their frequency. The vast majority started ART with stavudine, lamivudine, and nevirapine [852 (82.9%)], with the second most utilized ART regimen being stavudine, lamivudine, and efavirenz [117 (11.3%)]. At 24 months, the final regimen (Table 5) differed from the initial regimen in 304 (29.2%) of the 1040 patients, with 71% of the changes being single drug substitutions. Only 5 patients (0.5%) switched to regimens that were considered second-line treatment options by Rwanda national protocols: 1 switch was due to medicine side effects and 4 to ART treatment failure. Of the 4 patients with treatment failure, 2 switched to the second-line regimen of tenofovir, lamivudine, and lopinavir/ritonavir and 2 patients switched to tenofovir, abacavir, and lopinavir/ritonavir.
TB was diagnosed in 185 patients (17.8%), of which 121 started TB treatment before ART, 6 concurrently with ART, and 58 after ART (48 between the start and year 1 of ART, and 10 between year 1 and 2 of ART). Of the 185 patients diagnosed with active TB, 170 had recorded final TB outcomes as follows: 152 (89.4%) were either cured or completed treatment, 13 (7.6%) died, 1 (0.6%) defaulted, and 4 (2.4%) transferred out. In the multivariate analysis, there was no association between diagnosis of TB and attrition from care.
The outcomes of this study demonstrate that ART programs in rural resource-poor areas of Africa can have high retention rates (92.3%) after 2 years of care. Our report compares favorably to a recent estimate of the proportion of all-cause adult patient attrition from ART programs in service delivery settings in sub-Saharan Africa, where a systematic review of 39 cohorts and 226,307 patients revealed a 24-month retention of 70.0% (range: 66.7%–73.3%).18 The low loss to follow-up (2.7%), low mortality rate (5.0%), and high rate of plasma HIV viral suppression (97.5% less than 500 copies/mL) of this cohort are among the best reported in Africa and worldwide.2,3,18–22
This community-based ART program, implemented according to the Rwanda MoH protocols in rural public health clinics with additional support strategies from PIH, was specifically designed to improve HIV/TB treatment adherence and retention. Although daily medication adherence was not measured in the present study, the excellent virologic outcomes at 24 months suggest a high level of sustained adherence.
A systematic review by Hart et al23 demonstrated that directly observed ART was associated with improved virologic, immunologic, and adherence outcomes. In Rwanda, CHW “accompagnateurs” visit patients in their homes to supervise treatment, ensuring they take their medications regularly and correctly. Over time, the CHWs teach their patients how to manage complex treatments, cope with side effects, and identify the signs and symptoms of impending illness. They also provide ongoing social support and companionship, which may serve to reduce stigma and social isolation, thereby further promoting adherence.24
Numerous studies conducted in resource-limited settings have demonstrated that structural barriers such as food insecurity, transportation costs, user fees, and other patient “out of pocket” health costs negatively impact medication and visit adherence.25–29 The “accompaniment” model employed here enhances the provision of community-based directly observed therapy of ART with targeted social and material supports designed to remediate barriers to adherence and retention common in impoverished rural communities. The model was based on the PIH HIV Equity Initiative, launched in rural Haiti in 2000,30,31 which has been successfully replicated in Peru, Malawi, Lesotho, Rwanda, and the United States.11 Although favorable outcomes have been demonstrated at several sites, the current report is the first large-scale evaluation of the accompaniment model in sub-Saharan Africa.32
The most common regimen changes were single-drug substitutions, usually to manage side-effects or changes involving issues of drug interactions when patients initiated or ended TB treatment. The most common substitutions were zidovudine or tenofovir for stavudine in cases of stavudine intolerance and efavirenz to nevirapine upon completion of antituberculous treatment for HIV/TB-coinfected patients. At 24 months, only 4 patients (0.4%) had changed to a second-line ART regimen as a result of treatment failure.
For HIV/TB-coinfected patients, TB treatment success (cure/completed) rate was also high (89.4%), with only 1 patient (0.6%) defaulting from TB treatment. In addition, TB screening (Box 1) done at the start of ART seems to have detected a relatively high level of coinfection with 121 (12.2%) of patients starting TB therapy before or at the time of initiation of ART. Molecular diagnostic methods and culture were not part of this community-based ART program; adding these may result in diagnosis of TB more accurately and effectively.
Of note, the community-based ART program described here was set within a highly effective national HIV care and treatment program, which has become increasingly integrated with the primary health system. Since January 2004, the Government of Rwanda has been committed to universal free access to HIV care and has backed that commitment with increased investment in the health system, strengthening human resources, infrastructure, medical commodities and services.33 A recent retrospective cohort analysis of randomly selected adults in the Rwandan HIV program demonstrated a retention rate of 86% with low mortality (4.6%) and loss to follow-up (4.9%) at 12 months.34
The additional cost of the comprehensive accompaniment model was estimated at US $630 per patient per year for the first year and then US $340 per year thereafter, with the nutritional support, the primary cost driver in the first year of treatment and community-based daily visit component costing US $128 per patient per year (Beth Collins, MBA, Clinton Foundation HIV/AIDS initiative, unpublished data, October 2006). Although this represents a substantial investment, the excellent virologic outcomes and long-term retention could prove to be well worth the investment in terms of cost effectiveness.
The majority of the deaths occurred soon after the initiation of ART, which is consistent with other studies.2,3 As men with advanced disease had higher attrition from care, culturally appropriate interventions both to entice men into care and to retain men in care will have to be entertained. Women have many opportunities for HIV testing, including family planning and antenatal care visits, which may induce them into treatment at an earlier stage. Advanced age in our study was associated with attrition from care; whereas in a review of 18 published cohort studies, Lawn et al3 found that in contrast to data from high-income settings, increasing age was associated with higher mortality risk in only one of the reviewed cohorts.35 A recent report from Malawi also saw decreased survival with patients older than 60 years.36
Though the overall treatment retention rate at 24 months was excellent, loss to follow-up rates were higher among those enrolling in year 2006. Possible explanations for this could include challenges with scale-up in both increasing the number of patients receiving ART at a site and growing services in rural sites at greater distances from the hospital. However, no differences in loss to follow-up were seen by treatment site. Further analysis and long-term follow-up is warranted to investigate this finding, as other reports have demonstrated declines in retention as programs are scaled-up.37
This study has a number of limitations. Because this retrospective study utilized routinely collected clinical information, data completeness was low for many variables, such as follow-up CD4 T-cell count and weight. Our decision to adhere to strict definitions of “year 1” and “year 2” T-cell counts and weights may have also contributed to the data completeness issues. Social factors often associated with adherence and retention in care, such as alcohol or other substance use,38 were recorded on fewer than half of patients in the medical records, and therefore, we were unable to assess the influence of these factors. Patients with a documented transfer to an ART treatment site outside of the accompaniment program's catchment area were considered retained in care; it was not documented at their 2-year anniversary they were still in care at the facility to which they transferred. Although this number was relatively small (3.4% of the total cohort), it could result in a slight overestimate of the number of patients retained in care at 2 years. In addition, there is a possibility of selection bias toward more motivated patients, patients willing to enter a novel community-based program. Viral loads were only done on a small subset (26%) of the patients and may not be fully representative of the whole group. Last, the descriptive nature of this report precludes us from making formal comparisons with other programs, and the study was not designed to differentiate the impact of different program components on treatment outcomes.
A program of intensive community-based treatment support for ART in rural Rwanda had very high success at retaining people in care at 2 years with very low rates of loss to follow-up and death. This study reinforces published evidence demonstrating that HIV treatment outcomes in resource-limited settings can match or exceed those in wealthy countries, but also demonstrates that excellent results can be sustained in a large program. Having committed to improving access to HIV treatment in sub-Saharan Africa, the international community should set quality benchmarks for country HIV programs; a goal of 90% long-term treatment retention might be one such goal. Preserving the intensity of support and quality of care as the program grows in size and longevity remains a critical challenge. As demonstrated in Rwanda, excellent results may be achieved with coordinated national planning, good governance, adequate resources, and a strong underlying health system. Although the accompaniment model of community-based ART has produced excellent treatment outcomes, further study is warranted to determine the relative impact of individual program components to facilitate targeting of adherence support interventions in settings of resource scarcity.
We would like to thank the patients, CHWs, and health care providers who comprised the community-based ART program in the southern Kayonza District and Kirehe Districts. We acknowledge the contributions of the following individuals to this article: Melissa Gilloolly, Patrick Manyika, and Minda Nicolas. We wish to acknowledge the leadership of the Rwandan MoH and the generous support of the Clinton Health Access Initiative and the World Food Program.
1. Joint United Nations Programme on HIV/AIDS. AIDS at 30: Nations at a Crossroads. Geneva, Switzerland:Joint United Nations Programme on HIV/AIDS; 2011.
2. Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med. 2007;4:e298.
3. Lawn SD, Harries AD, Anglaret X, et al.. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008;22:1897–1908.
4. Djomand G, Roels T, Ellerbrock T, et al.. Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Cote d'Ivoire. AIDS. 2003;17:(suppl 3):S5–S15.
5. Laurent C, Kouanfack C, Koulla-Shiro S, et al.. Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial. Lancet. 2004;364:29–34.
6. Koenig SP, Leandre F, Farmer PE. Scaling-up HIV treatment programmes in resource-limited settings: the rural Haiti experience. AIDS. 2004;18:(suppl 3):S21–S25.
7. Bekker LG, Myer L, Orrell C, et al.. Rapid scale-up of a community-based HIV treatment service: programme performance over 3 consecutive years in Guguletu, South Africa. S Afr Med J. 2006;96:315–320.
8. Laurent C, Diakhate N, Gueye NF, et al.. The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study. AIDS. 2002;16:1363–1370.
9. Zachariah R, Teck R, Buhendwa L, et al.. Community support is associated with better antiretroviral treatment outcomes in a resource-limited rural district in Malawi. Trans R Soc Trop Med Hyg. 2007;101:79–84.
10. Weidle PJ, Malamba S, Mwebaze R, et al.. Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' response, survival, and drug resistance. Lancet. 2002;360:34–40.
11. Partners In Health. Partners In Health 2009 Annual Report: Accompaniment: Solidarity in Action,. Boston, MA: Partners In Health; 2009.
12. United Nations Development Program. Human Development Report 2009: Rwanda. New York, NY: United Nations Development Program; 2009.
13. Ministry of Health, Rwanda National Institute of Statistics, Rwanda ICF Macro. Rwanda Interim Demographic and Health Survey 2007–2008. Calverton, MD: ICF Macro; 2009.
14. Rwanda Ministry of Health. TRAC ART Report for November 2009. Kigali, Rwanda: Rwanda Ministry of Health; 2009.
15. Rwanda Ministry of Health. HIV-AIDS in Rwanda: 2010 Epidemiologic Update. Kigali, Rwanda: Ministry of Health, Rwanda; 2010.
16. Rwanda Ministry of Health. Guide pour la Prise en Charge therapeutique du VIH/SIDA (Rwanda National Care and Treatment Guidelines). Kigali, Rwanda: Ministry of Health, Rwanda; 2005.
17. Hosmer D, Lemeshow S. Applied Logistic Regression. 2nd ed. New York, NY: Wiley Interscience Inc; 2000.
18. Fox MP, 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:(suppl 1):1–15.
19. Chi BH, Yiannoutsos CT, Westfall AO, et al.. Universal definition of loss to follow-up in HIV treatment programs: a statistical analysis of 111 facilities in Africa, Asia, and Latin America. PLoS Med. 2011;9:e1001111.
20. Mills EJ, Nachega JB, Buchan I, et al.. Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. JAMA. 2006;296:679–690.
21. Tassie JM, Baijal P, Vitoria MA, et al.. Trends in retention on antiretroviral therapy in national programs in low-income and middle-income countries. J Acquir Immune Defic Syndr. 2010;54:437–441.
22. Barnighausen T, Chaiyachati K, Chimbindi N, et al.. Interventions to increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation studies. Lancet Infect Dis. 2011.
23. Hart JE, Jeon CY, Ivers LC, et al.. Effect of directly observed therapy for highly active antiretroviral therapy on virologic, immunologic, and adherence outcomes: a meta-analysis and systematic review. J Acquir Immune Defic Syndr. 2010;54:167–179.
24. Behforouz HL, Farmer PE, Mukherjee JS. From directly observed therapy to accompagnateurs: enhancing AIDS treatment outcomes in Haiti and in Boston. Clin Infect Dis. 2004;38:(suppl 5):S429–S436.
25. Geng EH, Nash D, Kambugu A, et al.. Retention in care among HIV-infected patients in resource-limited settings: emerging insights and new directions. Curr HIV/AIDS Rep. 2010;7:234–244.
26. Franke MF, Murray MB, Munoz M, et al.. Food insufficiency is a risk factor for suboptimal antiretroviral therapy adherence among HIV-infected adults in urban Peru. AIDS Behav. 2010.
27. Ivers LC, Chang Y, Gregory Jerome J, et al.. Food assistance is associated with improved body mass index, food security and attendance at clinic in an HIV program in central Haiti: a prospective observational cohort study. AIDS Res Ther. 2010;7:33.
28. Tuller DM, Bangsberg DR, Senkungu J, et al.. Transportation costs impede sustained adherence and access to HAART in a clinic population in southwestern Uganda: a qualitative study. AIDS Behav. 2010;14:778–784.
29. Beauliere A, Toure S, Alexandre PK, et al.. The financial burden of morbidity in HIV-infected adults on antiretroviral therapy in Cote d'Ivoire. PLoS One. 2010;5:e11213.
30. Farmer P, Leandre F, Mukherjee JS, et al.. Community-based approaches to HIV treatment in resource-poor settings. Lancet. 2001;358:404–409.
31. Walton DA, Farmer PE, Lambert W, et al.. Integrated HIV prevention and care strengthens primary health care: lessons from rural Haiti. J Public Health Policy. 2004;25:137–158.
32. Munoz M, Finnegan K, Zeladita J, et al.. Community-based DOT-HAART accompaniment in an urban resource-poor setting. AIDS Behav. 2010;14:721–730.
33. TRAC Report on the Evaluation of Clinical and Immunologic Outcomes from the National Antiretroviral Treatment Program in Rwanda, 2004–2005. Kigali, Rwanda: Ministry of Health, Rwanda; 2008.
34. Lowrance DW, Ndamage F, Kayirangwa E, et al.. Adult clinical and immunologic outcomes of the national antiretroviral treatment program in Rwanda during 2004–2005. J Acquir Immune Defic Syndr. 2009;52:49–55.
35. Toure S, Kouadio B, Seyler C, et al.. Rapid scaling-up of antiretroviral therapy in 10,000 adults in Cote d'Ivoire: 2-year outcomes and determinants. AIDS. 2008;22:873–882.
36. Negin J, van Lettow M, Semba M, et al.. Anti-retroviral treatment outcomes among older adults in Zomba district, Malawi. PLoS One. 2011;6:e26546.
37. Nglazi MD, Lawn SD, Kaplan R, et al.. Changes in programmatic outcomes during 7 years of scale-up at a community-based antiretroviral treatment service in South Africa. J Acquir Immune Defic Syndr. 2011;56:E1–E8.
38. Dahab M, Charalambous S, Hamilton R, et al.. “That is why I stopped the ART”: patients' & providers' perspectives on barriers to and enablers of HIV treatment adherence in a South African workplace programme. BMC Public Health. 2008;8:63.
antiretroviral therapy; CD4 lymphocyte count; community health worker; developing countries; HIV/AIDS; treatment outcome
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