Differences in Morbidity Between Breastfed HIV-Exposed Uninfected and HIV-Unexposed Infants in the Era of Universal Maternal Antiretroviral Therapy

Abstract

Background: HIV-exposed uninfected children (CHEU) experience higher morbidity and mortality than HIV-unexposed children (CHU), despite global scale-up of antiretroviral therapy (ART) in pregnancy. Evaluating the risk of morbidity in breastfed CHEU and CHU in the era of highly effective maternal ART and identifying socio-demographic characteristics associated with increased morbidity will inform future interventions to improve health in CHEU.Methods: Study participants included 172 CHEU and 164 CHU, born to enrolled pregnant women living with and without HIV, and followed through 12-months of age. Data on infant illness, along with information on additional biological and social factors, was collected via maternal report at all study visits. Differences in time to first episode of any illness and time of first episode of acute diarrhea (defined as ≥3 loose or watery stools per day) were assessed overall as well as stratified by HIV-exposure using adjusted hazard ratio (aHR) estimates (and corresponding 95% confidence intervals [CIs]) from multivariate Cox proportional hazards regression models. The final models for both primary outcomes included household food insecurity, maternal educational attainment, and breastfeeding duration, with the addition of maternal depression in the model for any illness, and marital status in the model for acute diarrhea. Results: Between birth and 12 months, children experienced 299 episodes of any illness (156 CHEU; 146 CHU) and 55 episodes of acute diarrhea (22 CHEU; 33 CHU). Overall, mothers reported optimal breastfeeding practices, with 86.9% still breastfeeding at their 12-month visit (83.7% CHEU; 90.2% CHU). In the adjusted model, HIV-exposure was not associated with first episode of any illness (aHR=1.06, 95% CI 0.83 – 1.36, p=0.640). However, it was associated with a decreased risk of acute diarrhea (aHR=0.36; 95% CI 0.30, 0.96; p=0.036). Moderate food insecurity (aHR=2.27, 95% CI 1.10, 4.67, p=0.026) and being previously married (aHR=2.24, 95% CI 1.16, 4.32, p=0.016) were associated with increased risk of acute diarrhea. Moderate-severe maternal depression was associated with an increased risk of any illness (aHR=1.94, 95% CI 1.00, 3.79, p=0.052). Conclusions: In contrast to earlier studies, CHEU experienced no difference in risk of illness and a decreased risk of acute diarrhea compared to CHU in the first 12-months of life. Future studies are needed to evaluate the effects of HIV prevention interventions and social support strategies on infant morbidity.