Background
The global scale-up of prenatal antiretroviral therapy (ART) has reduced the vertical transmission of HIV to <1%. In this context, a growing population of individuals with perinatal HIV exposure without infection (PHEU) has emerged, which now exceeds 20 million people worldwide. While growing evidence indicates that infants and children with PHEU are at increased risk of metabolic abnormalities, the long-term sequelae of in utero HIV/ART exposure into adulthood are largely unknown.
Methods
In this prospective observational study, we evaluated 41 young adults with PHEU and 41 young adults without HIV exposure or infection (24±5 y, 46% male per group). Young adults were matched 1:1 on ≥4 of the following: age, sex, race/ethnicity, maternal education, maternal substance use disorder, and breastfeeding. The primary outcome was BMI. Secondary outcomes were impaired glucose tolerance (HbA1c ≥5.7%, fasting glucose ≥100 mg/dL, and/or 2-hour glucose ≥140 mg/dL on oral glucose tolerance test), hypertension (clinical diagnosis, systolic blood pressure ≥140 mmHg, and/or diastolic blood pressure ≥90 mmHg), and hepatic steatosis (controlled attenuation parameter ≥263 dB/m on transient elastography). A composite metabolic comorbidity score was devised with 1 point given for each of the latter 3 outcomes. Linear mixed effect models and chi-square tests were used to estimate differences in metabolic endpoints by PHEU status.
Results
Young adults with PHEU had higher BMI (effect: 5.1 kg/m2; 95% CI, 1.7, 8.5 kg/m2) and prevalence of class 2-3 obesity (41% vs. 5%, P<0.0001) versus matched controls. Individuals with PHEU also had higher rates of impaired glucose tolerance (21% vs. 3%, P=0.01), hypertension (20% vs. 0%, P=0.003), and hepatic steatosis (44% vs. 15%, P=0.006), corresponding to a higher metabolic comorbidity score (effect: 0.66; 95% CI, 0.35, 0.98). PHEU remained independently associated with BMI and comorbidity score upon adjusting for young adult (e.g., adverse childhood experiences) and maternal (e.g., BMI) factors. PHEU also conferred a higher rate of at least 1 comorbidity in young adults with obesity (89% vs. 42%, P=0.004) and without obesity (31% vs. 4%, P=0.01).
Conclusions
In the oldest cohort studied to date, young adults with PHEU had a higher burden of severe obesity and metabolic comorbidities versus matched unexposed peers. Though targeting BMI may partially mitigate metabolic disease risk, adverse metabolic outcomes were more common in people with PHEU irrespective of obesity.