High Rates of All-cause and Gastroenteritis-related Hospitalization Morbidity and Mortality among HIV-exposed Indian Infants

Abstract

BackgroundHIV-infected and HIV-exposed, uninfected infants experience a high burden of infectious morbidity and mortality. Hospitalization is an important metric for morbidity and is associated with high mortality, yet, little is known about rates and causes of hospitalization among these infants in the first 12 months of life.MethodsUsing data from a prevention of mother-to-child transmission (PMTCT) trial (India SWEN), where HIV-exposed breastfed infants were given extended nevirapine, we measured 12-month infant all-cause and cause-specific hospitalization rates and hospitalization risk factors.ResultsAmong 737 HIV-exposed Indian infants, 93 (13%) were HIV-infected, 15 (16%) were on HAART, and 260 (35%) were hospitalized 381 times by 12 months of life. Fifty-six percent of the hospitalizations were attributed to infections; gastroenteritis was most common accounting for 31% of infectious hospitalizations. Gastrointestinal-related hospitalizations steadily increased over time, peaking around 9 months. The 12-month all-cause hospitalization, gastroenteritis-related hospitalization, and in-hospital mortality rates were 906/1000 PY, 229/1000 PY, and 35/1000 PY respectively among HIV-infected infants and 497/1000 PY, 107/1000 PY, and 3/1000 PY respectively among HIV-exposed, uninfected infants. Advanced maternal age, infant HIV infection, gestational age, and male sex were associated with higher all-cause hospitalization risk while shorter duration of breastfeeding and abrupt weaning were associated with gastroenteritis-related hospitalization.ConclusionsHIV-exposed Indian infants experience high rates of all-cause and infectious hospitalization (particularly gastroenteritis) and in-hospital mortality. HIV-infected infants are nearly 2-fold more likely to experience hospitalization and 10-fold more likely to die compared to HIV-exposed, uninfected infants. The combination of scaling up HIV PMTCT programs and implementing proven health measures against infections could significantly reduce hospitalization morbidity and mortality among HIV-exposed Indian infants.

Morbidity in relation to feeding mode in African HIV-exposed, uninfected infants during the first 6 mo of life: the Kesho Bora study

“…Although several studies have quantified differences in morbidity by feeding mode in HIV-exposed infants (16)(17)(18)(19), the potential drawback of reverse causality (i.e., mothers changing feeding mode in response to infant illness) has not been considered to our knowledge, and some studies did not distinguish between HIV-infected and -uninfected infants. Also, most published data were collected before the era of the antiretroviral-based prevention of mother-to-child-transmission during pregnancy and postpartum.…”

“…Infants diagnosed with HIV infection by 6 wk of age were not eligible for the analysis because of their high morbidity/mortality risk and the well-known association of infectious morbidity and breastfeeding (11,19,23).…”

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

“…Programs for vertical transmission prevention of HIV (VTP) have reduced vertical infection to well below 10% (5), therefore nearly 2 million HIV-exposed but uninfected (HEU) infants are born annually. 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.…”

Maternal HIV infection alters the immune balance in the mother and fetus; implications for pregnancy outcome and infant health

“…Whether this was because of the changes in immune responses in HIV-exposed infants, an increased exposure to pathological microbes in the environment of HIV-infected mothers or mixed and formula feeding is not fully understood [81,82]. Since the introduction of cART during pregnancy mortality rates are similar between HIV-exposed and unexposed infants [40]; however, an increased susceptibility to infections in HIV-exposed infants remains a concern [18,19,83,84]. Increased susceptibility to and hospitalization for bacterial lower respiratory tract infections is reported in HIV-exposed infants compared with unexposed infants [18,85,86].…”

“…Although cART during pregnancy decreases the risk of congenital and early postnatal CMV infection [88], higher incidence of congenital CMV is still reported in these infants and associated with microcephaly at birth [89,90]. Recently, a study from India described increased incidence of gastrointestinal infections in HIV-exposed infants compared with infants born to healthy women [84]. The underlying mechanism for this increased susceptibility to in particularly viruses is not well understood.…”