MON-696 Obesity and Metabolic Comorbidities in Young Adults with Perinatal HIV Exposure Without Infection

Abstract Disclosure: N. Chahal: None. A.K. Arpante: None. J.E. Johnson: None. C.A. Dash: None. M.W. Ockene: None. I. Zheng: None. A. Boutin: None. H. Lee: None. K.E. Corey: None. T.L. Stanley: None. S.K. Grinspoon: None. L.T. Fourman: None. Background: Over 1 million HIV-negative individuals are born to mothers with HIV annually. While mounting evidence indicates an increased risk of metabolic abnormalities among this population in early life, long-term sequelae of perinatal HIV exposure without infection (PHEU) into adulthood remain largely unknown. This study examined the prevalence and prenatal correlates of obesity and metabolic comorbidities in the oldest known cohort of young adults with PHEU versus matched unexposed controls. Methods: In this prospective study, we evaluated 41 young adults with PHEU and 41 controls matched 1:1 on ≥4 of the following factors: age, sex, race/ethnicity, maternal education, maternal substance use disorder, and breastfeeding. Obesity was defined as BMI ≥30 kg/m2 with elevated waist circumference (≥88 cm in females, ≥102 cm in males), or BMI >40 kg/m2. Metabolic comorbidities included impaired glucose tolerance (HbA1c ≥5.7%, fasting glucose ≥100 mg/dL, and/or 2-hour glucose ≥140 mg/dL on oral glucose tolerance test), insulin resistance (HOMA-IR ≥3), hypertension (clinical diagnosis, SBP ≥140 mmHg, and/or DBP ≥90 mmHg), dyslipidemia (total cholesterol ≥200 mg/dL, HDL-C <40 mg/dL, and/or triglycerides ≥150 mg/dL), and hepatic steatosis (controlled attenuation parameter ≥263 dB/m on elastography). A composite metabolic comorbidity score was derived with 1 point assigned to each of the 5 selected outcomes. Framingham 30-year risk of cardiovascular disease (CVD) was calculated. Prenatal history was ascertained via maternal interview and medical records. Results: Young adults with PHEU (24±5 y, 46% male) had higher rates of obesity (51% vs. 29%, P=0.04), impaired glucose tolerance (21% vs. 3%, P=0.01), insulin resistance (24% vs. 2%, P=0.004), hypertension (20% vs. 0%, P=0.003), dyslipidemia (46% vs. 15%, P=0.002), and hepatic steatosis (44% vs. 15%, P=0.006) compared to matched controls. These differences conferred a higher metabolic comorbidity score (1.5±1.4 vs. 0.3±0.7, P<0.001) and 30-year CVD risk (9.7% vs. 5.8%, P=0.02). Relationships of PHEU with BMI, comorbidity score, and CVD risk persisted upon adjusting for young adult (e.g., adverse childhood experiences) and maternal factors (e.g., BMI). PHEU was associated with a higher rate of ≥1 metabolic comorbidity in young adults with (100% vs. 58%, P=0.001) and without obesity (42% vs. 15%, P=0.04). In the PHEU group, lower maternal prenatal CD4 count was associated with higher adult CVD risk (ρ=-0.42, P=0.03). Conclusions: Young adults with PHEU bear a greater burden of obesity and metabolic comorbidities versus unexposed peers. Maternal HIV-related immune dysregulation may contribute to these outcomes. These findings highlight the critical role of the intrauterine environment in shaping adult cardiometabolic disease risk and may have broader implications for other groups including offspring of mothers with obesity. Presentation: Monday, July 14, 2025