HIV Viremia During Pregnancy and Neurodevelopment of HIV-Exposed Uninfected Children in the Context of Universal Antiretroviral Therapy and Breastfeeding A Prospective Study

Background: Elevated HIV viral load (VL) in pregnancy has been linked to increased risk of mortality, immunologic abnormalities, infectious morbidity and restricted growth among HIV-exposed uninfected (HEU) children, but little is known about effects on child development. Methods: HIV-infected women initiating lifelong antiretroviral therapy (ART; tenofovir + emtricitabine + efavirenz) antenatally were followed from first antenatal visit through delivery and with their breastfed infants postpartum. Cognitive, motor and expressive language development (Bayley Scales of Infant and Toddler Development-Third Edition; delay defined as score < 85) were assessed on a subset of HEU infants. HIV VL was measured at ART initiation, in third trimester and around delivery. Cumulative viremia in pregnancy was expressed as log 10 VL copies x year/ mL [ viremia copy-years (VCY)]. Relationships between VCY and development were examined after adjusting for socioeconomic, behavioral and psychosocial confounders. Results: Women (median pre-ART log 10 VL 4.1, CD4 349 cells/ mm3) commonly reported adverse social circumstances (44% informal housing, 63% unemployed, 29% risky drinking). Among 214 infants (median age, 13 months; 53% male; 13% born < 37 weeks' gestation), viremia predicted lower motor and expressive language, but not cognitive, scores in crude and adjusted analysis [per log 10 VCY increase, a beta (95% confidence interval [CI]): motor, -2.94 (-5.77 to -0.11); language, -3.71 (-6.73 to -0.69) and cognitive -2.19 (-5.02 to 0.65)]. Increasing VCY also predicted higher relative odds of motor delay [adjusted odds ratio (aOR): 3.32; 95% CI: 1.36-8.14) and expressive language delay (aOR: 2.79; 95% CI: 1.57-4.94), but not cognitive delay (aOR: 1.68; 95% CI: 0.84-3.34). Conclusions: Cumulative maternal HIV viremia in pregnancy may have adverse implications for HEU child development.