Early mortality in adults initiating antiretroviral therapy (ART) in low- and middle-income countries (LMIC): a systematic review and meta-analysis.
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.


RESULTS
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.
School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America. agupta25@jhmi.edu
Amita
A
Gupta
Girish
G
Nadkarni
Wei-Teng
WT
Yang
Aditya
A
Chandrasekhar
Nikhil
N
Gupte
Gregory P
GP
Bisson
Mina
M
Hosseinipour
Naveen
N
Gummadi
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data*; D002423:Cause of Death; D003906:Developing Countries / Q000191:economics* / Q000706:statistics & numerical data*; D015658:HIV Infections / Q000191:economics* / Q000401:mortality*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011203:Poverty / Q000191:economics* / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis