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In utero HIV exposure tied to obesity,
reactive airway disease in adolescence
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"In utero HIV exposure is linked to obesity and reactive airway disease in adolescence"
Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
Children exposed to HIV in utero but remaining uninfected (HEU) may pay a clinical price later in life, according to results of a rigorous case-control comparison in a Boston healthcare system [1]. By the time they reached adolescence, HEU children were more likely than HIV-unexposed children to be obese or have reactive airway disease (coughing, wheezing, shortness of breath). Lower third-trimester maternal CD4 count correlated with higher body mass index (BMI) in HEU adolescents.
Prenatal antiretroviral therapy (ART) has almost eliminated perinatal HIV transmission. But while HEU children may escape HIV, they often do not escape problems like impaired growth, mitochondrial toxicity, and immune upsets, noted the Massachusetts General Hospital researchers who conducted this study. Whether such problems translate into health setbacks later in life remained unknown until this analysis.
To find out, the research team used a patient registry to identify 50 HEU adolescents and young adults. All participants were born since 1990 and had records available after 13 years of age. The researchers used the same registry to identify 141 non-HEU controls matched to HEU participants by birth date (+/-5 years), age at last encounter (+/-2 years), sex, race/ethnicity, and zip code. The Mass General investigators standardized BMI for age and sex. They defined obesity as BMI at or above 30 kg/m2 or at or above the 95th percentile. Maternal data were available for 48 HEU participants and 73 non-HEU controls.
The HEU group and controls had median ages of 18 and 19 years at last encounter, 54% and 55% were male, 40% and 40% black, and 30% and 31% Hispanic. Median household income stood at $57,391 in the HEU group and $57,143 in controls. HEU mothers and control mothers had median ages of 30 and 27 at delivery and median BMIs of 26 and 27. Twelve of 48 HEU mothers were obese during pregnancy. HEU mothers had taken ART for only a median 0.7 year.
The researchers identified reactive airway disease in 40% of HEU adolescents/young adults and 24% of controls, a significant difference (P = 0.04). HEU and control obesity rates were 42% and 25% (P = 0.04), and adolescent BMI z-scores averaged 1.1 and 0.7 (P = 0.03).
Linear regression saw an inverse correlation between maternal third-trimester CD4 count and adolescent HEU BMI z-score (the lower the CD4 count, the higher the BMI, r = -0.47, P = 0.01). The relationship remained robust after adjustment for prenatal maternal age, BMI, antiretroviral class, HIV duration, and median household income. Odds of obesity in HEU adolescents were 8-fold higher with a maternal third-trimester CD4 count below 250 (odds ratio 8.2, 95% confidence interval 1.5 to 54.9). In this analysis maternal viral load above 400 copies did not predict adolescent obesity.
The researchers proposed that the association between low maternal CD4 count and adolescent obesity "suggests a direct biologic link between in utero HIV exposure and long-term metabolic health among uninfected offspring." They believe these are the first findings indicating higher risk of obesity and metabolic disease in HEU.
Reference
1. Fourman LT, Gerard ME, Pan CS, Triant V, Stanley TL, Grinspoon SK. In utero HIV exposure is linked to obesity and reactive airway disease in adolescence. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 795.
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