Early Weaning of HIV-Exposed Uninfected Infants and Risk of Serious Gastroenteritis: Findings from Two Perinatal HIV Prevention Trials in Kampala, Uganda

Abstract

Objective To assess serious gastroenteritis risk and mortality associated with early cessation of breastfeeding in infants enrolled in two prevention-of-maternal-to-child-HIV-transmission trials in Uganda. Methods We used hazard rates to evaluate serious gastroenteritis events by month of age and mortality among HIV-exposed uninfected infants enrolled in the HIVNET 012 (1997-2001) and HIVIGLOB/NVP (2004-2007) trials. HIV-infected mothers were counseled using local infant feeding guidelines current at the time. Results Breastfeeding cessation occurred earlier in HIVIGLOB/NVP compared to HIVNET 012 (median 4.0 vs. 9.3 months, p<0.001). Rates of serious gastroenteritis were higher in HIVIGLOB/NVP (8.0/1000 child-months) compared to HIVNET 012 (3.1/1000 child-months; p < 0.001). Serious gastroenteritis events also peaked earlier at 3-4 and 7-8 months (16.2/1000 and 15.0/1000 child-months, respectively) compared to HIVNET 012 at 9 to10 months (20.8/1000 child-months). All cause-infant mortality did not statistically differ between the HIVIGLOB/NVP and the HIVNET 012 trials [3.2/1000 versus 2.0/1000 child-months respectively, (p=0.10)] Conclusion Early breastfeeding cessation seen in the HIVIGLOB/NVP trial was associated with increased risk of serious gastroenteritis among HIV-exposed uninfected infants when compared to later breastfeeding cessation in the HIVNET 012 trial. Testing interventions which could decrease HIV transmission through breastfeeding and allow safe breastfeeding into the second year of life are urgently needed.

Current Knowledge and Future Research on Infant Feeding in the Context of HIV: Basic, Clinical, Behavioral, and Programmatic Perspectives

“…In Uganda, a mean duration of any breastfeeding of 4.0 mo compared to 9.3 mo in a later trial was associated with higher rates of severe gastroenteritis (8.0 vs. 3.1 episodes/1000 child-months; P < 0.001) (45). Similarly, cessation of breastfeeding by 6 mo of age compared to prolonged breastfeeding in Malawi resulted in greater rates of hospitalization for gastroenteritis (2.9 vs. 0.1% at 7-9 mo and 1.6 vs. 0.2% at 10-12 mo; P < 0.001) and higher gastroenteritis related mortality (19 vs. 7/1000 infants at 9 mo and 24 vs. 12/1000 infants at 12 mo; P = 0.0002) (46).…”

“…higher viral load in milk with abrupt weaning, inadequate nutritional intake thereafter, death) outweighed the health benefits of PMTCT (51,83,84). Data from a number of other studies also support these findings (45,46). Women are now advised to stop breastfeeding gradually within a month (7).…”

“…Although the risk of HIV transmission continues for as long as breastfeeding continues (32), HIV-free survival of HIV-exposed infants who breastfed beyond 6 mo was similar to that of infants who received no breast milk after 6 mo (86,87). Infants given replacement foods after a period of breastfeeding also suffered increased serious infections, including diarrhea and pneumonia, growth faltering, and death (45)(46)(47)50,51,58). The importance placed on maximizing an infant's continued access to breast milk in the 2010 recommendations reflects the immunological benefits of breast milk as well as the importance of breast milk in providing adequate nutrition to infants > 6 mo of age.…”

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

“…Recent evidence indicates that HEU infants are at a higher risk of infectious morbidity and mortality than their HIV-unexposed, uninfected (HUU) peers (6)(7)(8)(9)(10)(11)(12). The underlying reason(s) for this phenomenon are still unclear but are possibly multifactorial; severity of maternal HIV disease (13), avoidance of breastfeeding (14)(15)(16), and differences in microbial exposures (17) have all been postulated. Furthermore, exposure to HIV itself (18), as well as to antiretroviral drugs for VTP, may also directly impact the HEU infant's immune system (19,20).…”

Maternal and infant health is protected by antiretroviral drug strategies that preserve breastfeeding by HIV-positive women

“…6 There are several other studies, including numerous studies from South Africa. [7][8][9][10][11][12][13][14] The consistency of the findings across diverse settings, across different study designs and with established biological processes makes it highly unlikely that the dangers of formula can be explained away as part of the vagaries of clinical research methodology. The findings of these studies, in conjunction with research findings demonstrating the efficacy of ARVs to significantly reduce the risk of HIV infection through breastfeeding, iteratively led the WHO to revise its recommendations from a position of recommending formula feeds as the default feeding practice for HIV-infected mothers, to recommending breastfeeding with ARVs.…”