Objectives

To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed, uninfected infants.

Design

Secondary data analysis of The Breastfeeding, Antiretrovirals, and Nutrition (BAN) clinical trial.

Methods

BAN randomized 2369 mother–infant pairs to maternal, infant, or no extended antiretroviral prophylaxis during breastfeeding. Morbidity outcomes examined were pneumonia/serious febrile illness, diarrhea/growth faltering, and malaria. Infant death was defined as neonatal (≤ 30 days of life), and postneonatal (31 days to 48 weeks of life). Cox proportional hazards models were used to evaluate the effect of covariates on infant morbidity and mortality.

Results

The rate of pneumonia/serious febrile illness was highest in the first 12 weeks (0.83/100 person-weeks) before rapidly decreasing; rates of all morbidity outcomes increased after 24 weeks. Rates of pneumonia/serious febrile illness and diarrhea/growth faltering were higher during the rainy season. Prophylactic infant cotrimoxazole significantly decreased the rates of all morbidity outcomes. White blood cell (WBC) count less than 9000/μl at birth was associated with increased diarrhea/growth faltering [adjusted hazard ratio (aHR) 1.73, P = 0.04] and malaria (aHR 2.18, P = 0.02). Low birth weight (2000–2499 g) was associated with neonatal death (aHR 12.3, P <0.001). Factors associated with postneonatal death included rainy season (aHR 4.24, P = 0.002), infant cotrimoxazole (aHR 0.48, P = 0.03), and low infant WBC count at birth (aHR 2.53, P = 0.02).

Conclusion

Infant morbidity rates increased after 24 weeks, when BAN infants weaned. Introduction of prophylactic cotrimoxazole was associated with reduced rates of morbidity and mortality in HIV-exposed uninfected infants. Unexpectedly, a low WBC count at birth was significantly associated with later infant morbidity and mortality in this cohort.