High Burden of Morbidity and Mortality but Not Growth Failure in Infants Exposed to but Uninfected with Human Immunodeficiency Virus in Tanzania

Abstract

Objective: To compare health and growth outcomes in children infected with HIV, children exposed to but uninfected with HIV, and children unexposed to HIV.

Study design: Our cohort included 3554 Tanzanian children enrolled in 2 trials of micronutrient supplementation. Among infants born to mothers infected with HIV, 264 were infected with HIV and 2088 were exposed to but uninfected at 6 weeks of age. An additional 1202 infants were unexposed to HIV. Infants were followed until 18 months of age, death, or loss to follow-up. Morbidity and growth were assessed at monthly nurse visits.

Results: Compared with unexposed infants, hazard ratios (95% CI) for all-cause mortality in infants infected with HIV and infants who were exposed to but uninfected with HIV were 28.99 (14.83-56.66) and 2.79 (1.41-5.53), respectively, after adjusting for demographic and nutritional covariates. Compared with infants unexposed to HIV, infants infected with HIV also had a significantly greater risk of all measured morbidities, while infants who were exposed to but uninfected with HIV were significantly more likely to suffer from cough, fever, unscheduled outpatient visits, and hospitalizations. Infants infected with HIV also were more likely to experience stunting, wasting, and underweight at baseline and during follow-up. Infants exposed to but uninfected with HIV were more likely to be underweight at baseline (adjusted relative risk, 2.05; 95% CI, 1.45-2.89), but on average, experienced slower declines in height-for-age z-score, weight-for-age z-score, and weight-for-height z-score as well as a lower rate of stunting over follow-up, compared with unexposed infants.

Conclusion: In addition to preventing and treating HIV infection in infants, prevention-of-mother-to-child-transmission of HIV and child health services should also target children exposed to but uninfected with HIV to improve health outcomes in this vulnerable population.

Trial registration: Clinicaltrials.gov: NCT00197730 and NCT00421668.

Keywords: HIV; HIV-exposed-uninfected; child health; growth; morbidity; mortality.

Figure 1

Height-for-age, Weight-for-age and Weight-for-height Z-scores over time in HIV-positive, HIV-exposed-uninfected and HIV-unexposed Infants (adjusted for baseline covariates). Curves were creating using mixed effects models with restricted cubic splines with knots at 10 weeks and 3, 6, 9 12 & 15 months of age. The models are adjusted for maternal height and education, as well as infant sex and treatment group. The adjusted means presented here are for children who received placebo in the parent trial, live in a household with 1–3 assets and whose mother is the median height (156cm), is a housewife without income, and has 1–7 years of education. Bars represent 95% confidence intervals for each of the three groups at age 6 weeks and 6, 12 and 18 months.