Abstract
BackgroundA substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation.MethodsWe analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (n = 1815; body mass index [BMI] <18.5 kg/m2) were recruited at referral to ART and randomised to receive different nutritional supplements. Demographics, measures of body composition, blood electrolytes and clinical conditions were investigated as potential risk factors using Poisson regression models.ResultsThe mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63).ConclusionAmong malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population.Trial registrationPan African Clinical Trials Registry, PACTR201106000300631; registered on 1st June 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1894-3) contains supplementary material, which is available to authorized users.
Highlights
A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished
In our recent Nutritional Support for African Adults Starting Antiretroviral Therapy (NUSTART) trial we addressed malnutrition as a risk factor for mortality by randomizing underweight African adults initiating ART to a lipid-based nutritional supplement (LNS) containing
Well-established risk factors we found consistent with previous studies [4, 6, 9] include low body mass index (BMI), low fat-free mass, low CD4, high C-reactive protein (CRP), and male sex
Summary
A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. Consistent risk factors for early mortality include delayed ART initiation, indicated by. In our recent Nutritional Support for African Adults Starting Antiretroviral Therapy (NUSTART) trial we addressed malnutrition as a risk factor for mortality by randomizing underweight African adults initiating ART to a lipid-based nutritional supplement (LNS) containing. While we observed no difference in mortality between treatment arms, the trial design provided a unique opportunity for detailed clinical assessments of malnourished, HIV-infected persons both prior to ARTinitiation and during the early months of treatment [10, 11]. Many studies have reported mortality risk factors among patients starting ART but, as far as we know, none has included the high-risk period between referral for ART and starting ART in a large cohort of malnourished patients. Given the very high mortality observed, we felt it important to analyse further the extensive NUSTART database, including clinical conditions, blood electrolytes and body composition, to determine risk factors that could be used to improve clinical understanding and management of this vulnerable population
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