Impact of HIV exposure without infection on hospital course and 30-day mortality among young children in sub-Saharan Africa: a multi-site cohort study

Abstract Background: HIV-exposed uninfected (HEU) young children are at increased risk of hospitalization and death as compared to HIV-unexposed uninfected (HUU) children. The drivers of poor outcomes among HEU children remain unknown, limiting the development of interventions to support this vulnerable population. Methods: We performed a secondary analysis of data from a large multi-country prospective cohort Childhood Acute Illness and Nutrition (CHAIN) Network study. Hospitalized children aged 2-23 months were followed from an index admission for 6 months after discharge to determine acute and long-term outcomes. Data from the 5 sites in Uganda, Kenya, and Malawi were included. Using perinatal HIV exposure (HEU and HUU) as the primary exposure and adjusting for child, caregiver, and household characteristics, we compared 30-day survival outcomes, nutritional status, illness severity, and utilization of inpatient resources. Results: We included 1486 children: 217 HEU and 1269 HUU. Wasting and stunting were more frequent in HEU than HUU children, with adjusted OR 1.46, 95% CI (1.06-2.01) and adjusted OR 2.03, 95% CI (1.42 – 2.90), respectively. HEU children were twice as likely to have a prolonged hospital stay compared to HUU children adjusted OR 2.17, 95% CI (1.23- 3.80), despite no significant difference in the prevalence of severe illness at admission adjusted OR 1.25, 95% CI (0.88-1.77). Admission diagnoses and use of inpatient resources also did not differ significantly between groups. HEU children had an increased risk of mortality during the 30 days following hospital admission adjusted hazard ratio 1.75, 95% CI (1.09- 2.80). Conclusions: HEU childrenare more likely to be wasted and stunted, have prolonged hospital stay, and die within 30 days of hospitalization, as compared to HUU children. Hospitals in settings where maternal HIV infection remains common should ensure that maternal HIV status is established among children requiring admission and build capacity to provide additional hospital monitoring and early post-discharge support for HEU children.