Background:  Early weaning with replacement feeding for breastfeeding HIV-1-exposed infants is widely recommended for prevention of HIV mother-to-child transmission (MTCT). However, post-weaning, the infant can acquire gastroenteritis, leading to death because of the lack of clean water and utensils and inadequate nutrition. We assessed gastroenteritis frequency and mortality pre- and post-weaning in infants enrolled in an ART prophylaxis trial to prevent MTCT.

Methods:  An ongoing trial in Blantyre, Malawi (PEPI) randomizes infants HIV-uninfected at birth to 3 ART regimens. Mothers are counseled to exclusively breastfeed and then stop all breastfeeding at 6 months. Infants are seen at 1, 3, 6, 9, and 14 weeks and 6, 9, 12, 15, 18, and 24 months. Information on breastfeeding, gastroenteritis, hospitalization, and mortality was collected at all visits. Infant HIV status was determined by DNA polymerase chain reaction (PCR). This analysis evaluated age-specific gastroenteritis frequency to age 12 months among infants HIV-uninfected at the visit in which gastroenteritis was reported. Cumulative probabilities of overall and gastroenteritis-related mortality were estimated using Kaplan-Meier analysis and compared to an earlier trial at the same site (NVAZ) where early weaning was not recommended (median breastfeeding, 732 days).        

Results:  The median duration of overall breastfeeding was 183 days. Among HIV-uninfected infants (all ART arms and breastfeeding modes combined), probability of gastroenteritis was 1.7% (27 of 1571) at 6 to 9 weeks, 2.6% (29 of 1096) at 3 months, 7.1% (63 of 893) at 6 months, 13.1% (77 of 590) at 9 months, and 9.0% (34 of 379) at 12 months. The frequency of at least 1 hospitalization with gastroenteritis was 2.4% (21 of 893) between ages 3 and 6 months and 3.1% (18 of 590) between 6 and 9 months. The cumulative overall and gastroenteritis-related mortality among the HIV-uninfected infants in the PEPI and NVAZ studies is shown in the table. Log-rank test for overall mortality was p = 0.04 and for gastroenteritis-related mortality, p = 0.0003

Conclusions:  Gastroenteritis frequency in PEPI was highest immediately following weaning. Gastroenteritis-related mortality was higher in PEPI than in NVAZ, an earlier trial conducted in same clinic, but without early weaning. Counseling strategies to assist mothers in safe preparation of nutritional weaning foods in resource-limited settings are urgently needed.