In utero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study.

OBJECTIVES: To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n = 100) and children who were HIV-exposed but uninfected (CHEU, n = 101). METHODS: Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine ± zidovudine (sdNVP ± ZDV), nevirapine + zidovudine + lamivudine (sdNVP + ZDV + 3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. RESULTS: Among CPHIV children, cART (SMD = -0.82, 95% CI: -1.37 to -0.28) and sdNVP ± ZDV (SMD = -0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12 months. Intrapartum sdNVP + ZDV + 3TC vs. no IPA predicted executive dysfunction (SMD = 0.80, 95% CI: 0.30-1.31), SEA problems (SMD = 0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD = -0.36, 95% CI: -0.75-0.02) over 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33). CONCLUSIONS: Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Quality of life among perinatally HIV-affected and HIV-unaffected school-aged and adolescent Ugandan children: a multi-dimensional assessment of wellbeing in the post-HAART era.

OBJECTIVE: To examine quality of life (QOL) in perinatally HIV-infected (PHIV) or HIV-exposed uninfected (PHEU) vs. healthy HIV-unexposed uninfected (HUU) children during school-age/adolescence. METHODS: PHIV infection was diagnosed via DNA PCR. Current HIV status was confirmed by HIV rapid diagnostic test. Three HIV groups were defined: PHIV, PHEU, and HUU. QOL was assessed with proxy and self-report versions of the PedsQL™ 4.0 instrument at 6-18 years of age. QOL scores ranged from zero (least QOL) to 100 (highest QOL) in the following dimensions: combined QOL inventory (CQOLI), multi-dimensional vigor (MDV), general wellbeing (GWB), present functioning, and general cognitive functioning (CF). Multivariable linear regression models estimated HIV-related percent differences (ß) in QOL scores and 95% confidence intervals (CI). FINDINGS: Compared to HUU CQOLI deficits ranged from 6.5 to 9.2% (95% CI -15.4, -1.6), GWB deficit ranged from 6.5 to 10.5% (95% CI -16.0, -1.3), MDV deficit ranged from 6.8 to 11.6% (95% CI -14.5, 0.9), and CF deficit ranged from 9.7 to 13.1% for PHIV children. QOL deficits of similar magnitude and direction in most domains were observed for PHIV compared to PHEU. However, self-reported indicators of GWB (ß = -3.5; 95% CI -9.0, 2.0) and present functioning (ß = 4.0; 95% CI -4.6, 12.5) were similar for PHIV compared to PHEU. QOL scores were generally similar for PHEU compared to HUU. CONCLUSION: PHEU and HUU had similar QOL profile but PHIV predicted sustained deficits in multiple QOL domains. PHIV and PHEU children were similar with respect to general wellbeing and present functioning. Psychosocial and scholastic interventions in combination with HIV care are likely to improve QOL in PHIV.