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      Early Mortality in Adults Initiating Antiretroviral Therapy (ART) in Low- and Middle-Income Countries (LMIC): A Systematic Review and Meta-Analysis

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          Abstract

          Background

          We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART) initiation in low- and middle-income countries (LMIC) in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known.

          Methods and Findings

          Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76%) from sub-Saharan Africa (SSA), 5 (10%) from Asia, 2 (4%) from the Americas, and 5 (10%) were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3–55 months and 11–192 cells/mm 3, respectively. Loss-to-follow-up, reported in 40 (80%) studies, ranged from 0.3%–27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11–0.24) versus 0.11 (95% CI 0.10–0.13) for Asia, and 0.07 (95% CI 0.007–0.20) for the Americas. Of 14 (28%) studies reporting cause-specific mortality, tuberculosis (TB) (5%–44%), wasting (5%–53%), advanced HIV (20%–37%), and chronic diarrhea (10%–25%) were most common. Independent factors associated with early mortality in 30 (60%) studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA.

          Conclusions

          Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are urgently needed.

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          Most cited references 68

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              An adjusted rank correlation test is proposed as a technique for identifying publication bias in a meta-analysis, and its operating characteristics are evaluated via simulations. The test statistic is a direct statistical analogue of the popular "funnel-graph." The number of component studies in the meta-analysis, the nature of the selection mechanism, the range of variances of the effect size estimates, and the true underlying effect size are all observed to be influential in determining the power of the test. The test is fairly powerful for large meta-analyses with 75 component studies, but has only moderate power for meta-analyses with 25 component studies. However, in many of the configurations in which there is low power, there is also relatively little bias in the summary effect size estimate. Nonetheless, the test must be interpreted with caution in small meta-analyses. In particular, bias cannot be ruled out if the test is not significant. The proposed technique has potential utility as an exploratory tool for meta-analysts, as a formal procedure to complement the funnel-graph.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                29 December 2011
                : 6
                : 12
                Affiliations
                [1 ]School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
                [2 ]Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
                [3 ]Johns Hopkins Clinical Trial Unit, Byramjee Jeejeebhoy Medical College, Pune, India
                [4 ]School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [5 ]School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
                Jiangsu University, China
                Author notes

                Conceived and designed the experiments: AG. Analyzed the data: AG AC GN NGupte WY NGummadi. Wrote the paper: AG WY AC NGupte NGummadi GB MH.

                PONE-D-11-12223
                10.1371/journal.pone.0028691
                3248405
                22220193
                Gupta et al. 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.
                Counts
                Pages: 11
                Categories
                Research Article
                Biology
                Microbiology
                Virology
                Antivirals
                Immunodeficiency Viruses
                Virulence Factors and Mechanisms
                Medicine
                Clinical Research Design
                Meta-Analyses
                Systematic Reviews
                Global Health
                Infectious Diseases
                Viral Diseases
                HIV
                HIV clinical manifestations
                HIV epidemiology

                Uncategorized

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