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      Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review

      1 , 2 , * , 1 , 2 , 3

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          In this systematic review, Sydney Rosen and Matthew Fox find that less than one-third of patients who tested positive for HIV, but were not eligible for antiretroviral therapy (ART) when diagnosed, were retained in pre-ART care continuously.



          Improving the outcomes of HIV/AIDS treatment programs in resource-limited settings requires successful linkage of patients testing positive for HIV to pre–antiretroviral therapy (ART) care and retention in pre-ART care until ART initiation. We conducted a systematic review of pre-ART retention in care in Africa.

          Methods and Findings

          We searched PubMed, ISI Web of Knowledge, conference abstracts, and reference lists for reports on the proportion of adult patients retained between any two points between testing positive for HIV and initiating ART in sub-Saharan African HIV/AIDS care programs. Results were categorized as Stage 1 (from HIV testing to receipt of CD4 count results or clinical staging), Stage 2 (from staging to ART eligibility), or Stage 3 (from ART eligibility to ART initiation). Medians (ranges) were reported for the proportions of patients retained in each stage. We identified 28 eligible studies. The median proportion retained in Stage 1 was 59% (35%–88%); Stage 2, 46% (31%–95%); and Stage 3, 68% (14%–84%). Most studies reported on only one stage; none followed a cohort of patients through all three stages. Enrollment criteria, terminology, end points, follow-up, and outcomes varied widely and were often poorly defined, making aggregation of results difficult. Synthesis of findings from multiple studies suggests that fewer than one-third of patients testing positive for HIV and not yet eligible for ART when diagnosed are retained continuously in care, though this estimate should be regarded with caution because of review limitations.


          Studies of retention in pre-ART care report substantial loss of patients at every step, starting with patients who do not return for their initial CD4 count results and ending with those who do not initiate ART despite eligibility. Better health information systems that allow patients to be tracked between service delivery points are needed to properly evaluate pre-ART loss to care, and researchers should attempt to standardize the terminology, definitions, and time periods reported.

          Please see later in the article for the Editors' Summary

          Editors' Summary


          Since 1981, AIDS has killed more than 25 million people, and about 33 million people (mostly living in low- and middle-income countries) are now infected with HIV, the virus that causes AIDS. HIV gradually destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within ten years of infection. Then, in 1996, highly active antiretroviral therapy (ART) became available, and, for people living in developed countries, HIV infection became a chronic condition. Unfortunately, ART was extremely expensive, and HIV/AIDS remained a fatal illness for people living in developing countries. In 2003, governments, international agencies, and funding bodies began to implement plans to increase ART coverage in resource-limited countries. By the end of 2009, about a third of the people in these countries who needed ART (HIV-positive people whose CD4 count had dropped so low that they could not fight other infections) were receiving treatment.

          Why Was This Study Done?

          Unfortunately, many HIV-positive people in resource-limited countries who receive ART still do not have a normal life expectancy, often because they start ART when they have a very low CD4 count. ART is more successful if it is started before the CD4 count falls far below 350 cells/mm 3 of blood, the threshold recommended by the World Health Organization for ART initiation. Thus, if the outcomes of HIV/AIDS programs in resource-limited settings are to be improved, all individuals testing positive for HIV must receive continuous pre-ART care that includes regular CD4 counts to ensure that ART is initiated as soon as they become eligible for treatment. Before interventions can be developed to achieve this aim, it is necessary to understand where and when patients are lost to pre-ART care. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers investigate the retention of HIV-positive adults in pre-ART care in sub-Saharan Africa.

          What Did the Researchers Do and Find?

          The researchers identified 28 studies that included data on the proportion of adult patients retained between any two time points between testing positive for HIV and starting ART in HIV/AIDS care programs in sub-Saharan Africa. They defined three stages of pre-ART care: Stage 1, the interval between testing positive for HIV and receiving CD4 count results or being clinically assessed; Stage 2, the interval between enrollment in pre-ART care and the determination of eligibility for ART; and Stage 3, the interval between being deemed eligible for ART and treatment initiation. A median of 59% of patients were retained in Stage 1 of pre-ART care, 46% were retained in Stage 2, and 68% were retained in Stage 3. Retention rates in each stage differed greatly between studies—between 14% and 84% for Stage 3 pre-ART care, for example. Because the enrollment criteria and other characteristics of the identified studies varied widely and were often poorly defined, it was hard to combine study results. Nevertheless, the researchers estimate that, taking all the studies together, less than one-third of patients testing positive for HIV but not eligible for ART when diagnosed were retained in pre-ART care continuously.

          What Do These Findings Mean?

          These findings suggest that there is a substantial loss of HIV-positive patients at every stage of pre-ART care in sub-Saharan Africa. Thus, some patients receiving a positive HIV test never return for the results of their initial CD4 count, some disappear between having an initial CD4 count and becoming eligible for ART, and others fail to initiate ART after having been found eligible for treatment. Because only a few studies were identified (half of which were undertaken in South Africa) and because the quality and design of some of these studies were suboptimal, the findings of this systematic review must be treated with caution. In particular, the estimate of the overall loss of patients during pre-ART care is likely to be imprecise. The researchers call, therefore, for the implementation of better health information systems that would allow patients to be tracked between service delivery points as a way to improve the evaluation and understanding of the loss of HIV-positive patients to pre-ART care in resource-limited countries.

          Additional Information

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          Most cited references 32

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          Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review

          Objectives To estimate the proportion of all-cause adult patient attrition from antiretroviral therapy (ART) programs in service delivery settings in sub-Saharan Africa through 36 months on treatment. Methods We identified cohorts within Ovid Medline, ISI Web of Knowledge, Cochrane Database of Systematic Reviews and four conference abstract archives. We summarized retention rates from studies describing observational cohorts from sub-Saharan Africa reporting on adult HIV 1- infected patients initiating first-line three-drug ART. We estimated all-cause attrition rates for 6, 12, 18, 24, or 36 months after ART initiation including patients who died or were lost to follow-up (as defined by the author), but excluding transferred patients. Results We analysed 33 sources describing 39 cohorts and 226 307 patients. Patients were more likely to be female (median 65%) and had a median age at initiation of 37 (range 34–40). Median starting CD4 count was 109 cells/mm3. Loss to follow-up was the most common cause of attrition (59%), followed by death (41%). Median attrition at 12, 24 and 36 months was 22.6% (range 7%–45%), 25% (range 11%–32%) and 29.5% (range 13%–36.1%) respectively. After pooling data in a random-effects meta-analysis, retention declined from 86.1% at 6 months to 80.2% at 12 months, 76.8% at 24 months and 72.3% at 36 months. Adjusting for variable follow-up time in a sensitivity analysis, 24 month retention was 70.0% (range: 66.7%–73.3%), while 36 month retention was 64.6% (range: 57.5%–72.1%). Conclusions Our findings document the difficulties in retaining patients in care for lifelong treatment, and the progress being made in raising overall retention rates.
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            Early loss of HIV-infected patients on potent antiretroviral therapy programmes in lower-income countries.

            To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with (3) 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003-2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28-20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55-12.8) but not recorded death (HR: 1.02; 95% CI: 0.44-2.36). Compared with a baseline CD4-cell count (3) 50 cells/microl, a count < 25 cells/microl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43-4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23-1.77) and death (HR: 3.34; 95% CI: 2.10-5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97-16.05) and higher mortality (HR: 4.64; 95% CI: 1.11-19.41). Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries.
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              Retention in care among HIV-infected patients in resource-limited settings: emerging insights and new directions.

              In resource-limited settings--where a massive scale-up of HIV services has occurred in the last 5 years--both understanding the extent of and improving retention in care presents special challenges. First, retention in care within the decentralizing network of services is likely higher than existing estimates that account only for retention in clinic, and therefore antiretroviral therapy services may be more effective than currently believed. Second, both magnitude and determinants of patient retention vary substantially and therefore encouraging the conduct of locally relevant epidemiology is needed to inform programmatic decisions. Third, socio-structural factors such as program characteristics, transportation, poverty, work/child care responsibilities, and social relations are the major determinants of retention in care, and therefore interventions to improve retention in care should focus on implementation strategies. Research to assess and improve retention in care for HIV-infected patients can be strengthened by incorporating novel methods such as sampling-based approaches and a causal analytic framework.

                Author and article information

                [1 ]Center for Global Health and Development, Boston University, Boston, Massachusetts, United States of America
                [2 ]Health Economics and Epidemiology Research Office, Wits Health Consortium, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
                [3 ]Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America
                Duke University Medical Center, United States of America
                Author notes

                Conceived and designed the experiments: SR MPF. Performed the experiments: SR MPF. Analyzed the data: SR MPF. Contributed reagents/materials/analysis tools: SR MPF. Wrote the paper: SR MPF. ICMJE criteria for authorship read and met: SR MPF. Agree with the manuscript's results and conclusions: SR MPF. Wrote the first draft of the paper: SR.

                Role: Academic Editor
                PLoS Med
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                July 2011
                July 2011
                19 July 2011
                : 8
                : 7
                (Academic Editor)
                Rosen, Fox. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Pages: 16
                Research Article
                Infectious Diseases
                Viral Diseases
                HIV diagnosis and management
                Public Health
                Behavioral and Social Aspects of Health



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