Cognitive and language outcomes in HIV-uninfected infants exposed to combined antiretroviral therapy in utero and through extended breast-feeding

Objective:To determine whether there is a higher risk for cognitive or language delay among HIV-exposed uninfected (HEU) children exposed to cART (zidovudine/lamivudine/lopinavir/ritonavir) in utero and through 1 year of breast-feeding (World health Organization Option B+), compared with the control children born to HIV-uninfected mothers.Design:This is a double cohort study from Lusaka, Zambia.Methods:HEU (n=97) and control (n=103) children aged 15-36 months were assessed on their early nonverbal problem-solving and language skills using the standardized Capute Scales. A score of less than 85 on the Capute Full-Scale Developmental Quotient (FSDQ) was considered indicative of developmental delay and was the primary outcome of interest.Results:An FSDQ of less than 85 was found in eight (8.3%) of HEU participants and 15 (14.6%) of controls. In univariate logistic regressions, lower income [odds ratio (OR)=0.93, P=0.02], older infant age (OR=1.08, P=0.03), lower birth weight (OR=0.16, P<0.001), and less maternal education (OR=0.41, P=0.047) were associated with the probability of FSDQ less than 85, whereas Group (control/HEU) was not (OR=1.88, P=0.16). In the multivariable analysis, only lower birth weight (OR=0.15, P<0.001) remained associated with FSDQ less than 85.Conclusions:Our study did not support the presence of an adverse effect on cognitive and language development with prolonged antepartum and postpartum cART e/xposure. Larger studies and studies of older HEU children will be required to confirm these reassuring findings.