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.

The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children.

BACKGROUND: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. OBJECTIVE: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. METHODS: Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation. RESULTS: From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7-13.9) and 348,846copies/mL (IQR 160,941-681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96 weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10-8.32), p=0.03}; no difference was found among those with CD4 cell percent >5-14.9% and <5%. CONCLUSION: Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.

Adherence to tablet and liquid formulations of antiretroviral medication for paediatric HIV treatment at an urban clinic in Uganda.

BACKGROUND: Major obstacles remain in scaling up paediatric HIV treatment, including limited paediatric anti-retroviral drug options for resource-limited settings, challenges with adherence to liquid formulations and treatment fatigue with lifelong therapy. AIM: To determine levels of adherence to HAART in HIV-infected children at 12, 24, 36 and 48 weeks of follow-up and to compare adherence levels before and after switching from syrup to fixed-dose combination (FDC)-tablet anti-retroviral formulations. METHODS: HIV-infected children aged between 6 months and 12 years were initiated on anti-retroviral therapy at Makerere University-Johns Hopkins University Care Clinic, Kampala. Good adherence to HAART was defined as taking ≥95% of prescribed medications. Adherence levels were measured using pharmacy refill data, quarterly unannounced home-visit pill counts and caregiver self-reports. Data were analysed using STATA(®) version 10.0. RESULTS: A total of 129 HIV-infected children were initiated on HAART with 14.7% on syrups and 85.3% on tablet formulations at enrollment. According to caregiver self-reporting, 99.2%, 100%, 100% and 99.2% achieved ≥95% adherence at 12, 24, 36 and 48 weeks, respectively. Using pharmacy refill data, the proportions were 89.9%, 95.4%, 93.8% and 93.0% and for unannounced home visits were 89.8%, 92.4%, 88.9% and 86.2%, respectively. Median adherence to syrup formulations (97%, IQR 93-98) was significantly lower than for tablets (100%, IQR 97-100, p = 0.012, n = 28) using pharmacy refill data. Viral suppression correlated with home visit and pharmacy refill adherence data. CONCLUSION: The majority of children initiating HAART had good adherence when estimated by caregiver self-report and pharmacy refill data but lower adherence when measured by home-visit pill counts. Adherence to tablet formulation of HAART was significantly better than syrup formulation. Medication formulation did not significantly affect viral suppression.