SAT-256 Obesity and Reactive Airway Disease Are Increased Among HIV-Exposed Uninfected Adolescents

Abstract

Background: Worldwide, over 1 million babies are born to mothers with HIV each year. With the advent of prenatal antiretroviral therapy (ART), the vast majority of these individuals are HIV-exposed but uninfected (HEU). HEU infants and children exhibit impaired growth, mitochondrial toxicity, and immune activation compared to HIV-unexposed peers. Nonetheless, the long-term sequelae of in utero HIV and ART exposure have never before been examined. We hypothesized that in utero HIV/ART exposure may condition fetal development in a manner that predisposes to obesity and reactive airway disease (RAD) later in life. Methods: We leveraged a patient database registry at a U.S. academic health system to compare long-term health outcomes among HEU adolescents and matched controls, and to determine maternal factors associated with adverse HEU outcomes. HEU individuals born since 1990 with medical records available at age ≥ 13 y were identified. Over 200,000 controls also were retrieved from RPDR and matched up to 3:1 on birthdate (±5 y), age of last encounter (±2 y), sex, race, and zip code (SAS 9.4). Charts were manually reviewed to confirm HEU status and to extract health information. BMI was adjusted for age and sex per CDC growth charts. Obesity was defined as BMI ≥ 30 kg/m2 or ≥ 95 percentile. RAD was by clinical report. Results: 50 HEU adolescents (18 [15, 20] y, 54% male) and 141 matched controls (19 [16, 21] y, 55% male) were compared. Mothers of HEU adolescents were 30 ± 4 years old with BMI 26 [24, 30] kg/m2. Mothers had HIV for 4 [1, 7] years with CD4 count 405 [222, 615]/mm3, and 93% received prenatal ART. Obesity was seen in 42% of HEU adolescents compared to 25% of controls (P = 0.04). The prevalence of RAD also was higher among HEU than controls (40% vs. 24%, P = 0.04). Within the HEU group, there was a strong inverse correlation between maternal third trimester CD4 count and adolescent BMI z-score (r = -0.47, P = 0.01). This relationship persisted upon adjustment for prenatal maternal factors including age, BMI, ART, and HIV duration as well as median household income (P < 0.05). Lower third trimester CD4 count also was strongly associated with higher birth weight (r = -0.56, P = 0.006) and placental weight (r = -0.58, P = 0.006). Prenatal maternal CD4 nadir, peak HIV viral load, HIV duration, and ART were not associated with adolescent BMI z-score. Unlike obesity, maternal factors did not relate to RAD among HEU. Conclusions: In utero exposure to HIV/ART may predispose to obesity and RAD in adolescence. Lower prenatal maternal CD4 count – indicative of more severe immune dysfunction – was associated with higher adolescent BMI. Prospective studies are needed to further characterize metabolic and immune dysregulation among the aging and expanding HEU population. Insights learned from these individuals may have implications for other groups exposed to maternal inflammation in utero, including individuals born to obese mothers.