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      Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review

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          Abstract

          Background

          Long-term retention of patients in Africa's rapidly expanding antiretroviral therapy (ART) programs for HIV/AIDS is essential for these programs' success but has received relatively little attention. In this paper we present a systematic review of patient retention in ART programs in sub-Saharan Africa.

          Methods and Findings

          We searched Medline, other literature databases, conference abstracts, publications archives, and the “gray literature” (project reports available online) between 2000 and 2007 for reports on the proportion of adult patients retained (i.e., remaining in care and on ART) after 6 mo or longer in sub-Saharan African, non-research ART programs, with and without donor support. Estimated retention rates at 6, 12, and 24 mo were calculated and plotted for each program. Retention was also estimated using Kaplan-Meier curves. In sensitivity analyses we considered best-case, worst-case, and midpoint scenarios for retention at 2 y; the best-case scenario assumed no further attrition beyond that reported, while the worst-case scenario assumed that attrition would continue in a linear fashion. We reviewed 32 publications reporting on 33 patient cohorts (74,192 patients, 13 countries). For all studies, the weighted average follow-up period reported was 9.9 mo, after which 77.5% of patients were retained. Loss to follow-up and death accounted for 56% and 40% of attrition, respectively. Weighted mean retention rates as reported were 79.1%, 75.0% and 61.6 % at 6, 12, and 24 mo, respectively. Of those reporting 24 mo of follow-up, the best program retained 85% of patients and the worst retained 46%. Attrition was higher in studies with shorter reporting periods, leading to monthly weighted mean attrition rates of 3.3%/mo, 1.9%/mo, and 1.6%/month for studies reporting to 6, 12, and 24 months, respectively, and suggesting that overall patient retention may be overestimated in the published reports. In sensitivity analyses, estimated retention rates ranged from 24% in the worse case to 77% in the best case at the end of 2 y, with a plausible midpoint scenario of 50%.

          Conclusions

          Since the inception of large-scale ART access early in this decade, ART programs in Africa have retained about 60% of their patients at the end of 2 y. Loss to follow-up is the major cause of attrition, followed by death. Better patient tracing procedures, better understanding of loss to follow-up, and earlier initiation of ART to reduce mortality are needed if retention is to be improved. Retention varies widely across programs, and programs that have achieved higher retention rates can serve as models for future improvements.

          Abstract

          Almost half of people entering African HIV treatment programs were lost to follow-up or died within two years, according to this systematic review by Sydney Rosen and colleagues.

          Editors' Summary

          Background.

          About 25 million people in sub-Saharan Africa are infected with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). Every year, about three million more people become infected with HIV and 2 million die from AIDS in this region, where the pandemic has reduced life expectancy, orphaned many children, and reversed economic growth. Since 1996, HIV-positive people living in wealthier parts of the world have had access to cocktails of antiretroviral drugs that hold HIV in check and allow them to live relatively normal, healthy lives. But these drugs are expensive and it is only in the past five years that antiretroviral therapy (ART) programs have been initiated in sub-Saharan Africa, often with international support.

          Why Was This Study Done?

          For ART to work, HIV-infected individuals whose immune systems have been damaged by the virus have to take antiretroviral drugs regularly for the rest of their lives. If people take ART irregularly or stop taking their medications they may become sicker or die, or the viruses they carry may become resistant to antiretroviral drugs. Several studies have looked at how well patients on ART stick to their day-to-day medication schedules, but how long patients stay in treatment programs, which they must do to prevent illness and death from AIDS, has received little attention. In this study the researchers reviewed reports of whether patients stay in treatment in ART programs in sub-Saharan Africa, and also looked at the reasons why they drop out.

          What Did the Researchers Do and Find?

          The researchers identified 32 scientific reports published or presented at meetings between 2000 and 2007 that gave details of the proportion of adult patients retained (alive and receiving ART) in ART treatment programs (not including research studies) in 13 countries in sub-Saharan Africa. The average follow-up time of the programs (adjusted for number of patients in each) was 9.9 months. At this time, 77.5% of the patients were retained on average. Of the patients not retained, just under half had died and half had been lost to follow up. That is, they had missed clinic visits or had not picked up their medication. Estimated average retention rates at 6, 12, and 24 months were 79.08%, 75% and 61.6%, respectively; retention rates reported at 24 months ranged between 46% and 85% of patients. Finally, using sensitivity analysis (a technique that can estimate best- and worst-case possibilities), the researchers estimated that actual retention in ART programs after 2 years probably lies between one-quarter and three-quarters of patients.

          What Do These Findings Mean?

          These results show that roughly half of people starting HIV treatment programs in Africa are no longer receiving treatment after two years. The overall success rates of African treatment programs may actually be even lower, if one takes into account that programs with very low retention may be unlikely to publish their results. This study therefore indicates that a worrying number of patients in sub-Saharan Africa who need ART are lost from treatment programs. Because many of these patients are lost because they die from AIDS, one way to improve retention might be to start treating people with ART earlier, before they become seriously ill from HIV. Better efforts to find out exactly why patients drop out of programs (for example, the cost of drugs and/or of transport to clinics) might reduce the number of patients lost to follow up. The researchers also suggest that ART programs with very high retention rates might serve as models to improve retention rates in other programs.

          Additional Information.

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040298.

          • Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS

          • HIV InSite is a regional page on sub-Saharan Africa from the University of California, San Francisco

          • Information is provided by the US Centers for Disease Control and Prevention on the US President's Emergency Plan for AIDS Relief in various countries and regions

          • Avert is an international AIDS charity that provides information on HIV and AIDS in Africa

          • Aidsmap is an international AIDS organization that summarizes research about HIV/AIDS and reports news (in English, Spanish, Portuguese, French, and Russian)

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          Most cited references 48

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          Adherence to long-term therapies: evidence for action.

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            Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.

            The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians. To report on the feasibility and early outcomes of the program. Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system. Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines. Survival, regimen failure rates, and CD4 cell response. We enrolled 21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15,866 patients with documented World Health Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15,336 patients with a baseline result was 143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat. Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.
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              Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies.

              Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap. We analysed data on 12,574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group. FINDINGS During 24,310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/microL, adjusted hazard ratios were 0.74 (95% CI 0.62-0.89) for 50-99 cells/microL, 0.52 (0.44-0.63) for 100-199 cells/microL, 0.24 (0.20-0.30) for 200-349 cells/microL, and 0.18 (0.14-0.22) for 350 or more CD4 cells/microL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100,000 copies/microL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3.4% (2.8-4.1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43-58) in patients in the highest-risk strata. The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                pmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                October 2007
                16 October 2007
                : 4
                : 10
                Affiliations
                [1 ] Center for International Health and Development, Boston University School of Public Health, Boston, Massachusetts, United States of America
                [2 ] Health Economics Research Office, Wits Health Consortium, Johannesburg, South Africa
                [3 ] Infectious Diseases Section, Department of Medicine, Boston Medical Center, Boston, Massachusetts, United States of America
                Mexican National Institutes of Health, Mexico
                Author notes
                * To whom correspondence should be addressed. E-mail: sbrosen@ 123456bu.edu .
                Article
                07-PLME-RA-0170R2 plme-04-10-03
                10.1371/journal.pmed.0040298
                2020494
                17941716
                583838c6-ab86-4829-83bf-eefce7daf074
                This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
                Page count
                Pages: 11
                Categories
                Research Article
                Infectious Diseases
                Public Health and Epidemiology
                HIV Infection/AIDS
                Medicine in Developing Countries
                International Health
                Custom metadata
                Rosen S, Fox MP, Gill CJ (2007) Patient retention in antiretroviral therapy programs in sub-Saharan Africa: A systematic review. PLoS Med 4(10): e298. doi: 10.1371/journal.pmed.0040298

                Medicine

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