African Multi-Site 2-Year Neuropsychological Study of School-Age Children Perinatally Infected, Exposed, and Unexposed to Human Immunodeficiency Virus (original) (raw)
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AIDS (London, England), 2017
Children with HIV infection (HIV+) are at neuropsychological risk, but few studies have evaluated this at multiple sites in low and middle income countries (LMICs). We compared neuropsychological outcomes at enrollment (>5 yrs age) among HIV+, HIV-uninfected perinatally-exposed (HEU), and HIV unexposed (HU) children from 4 sub-Saharan countries. IMPAACT P1060 compared Nevirapine (NVP) versus Lopinavir/Ritonavir (LPVr)-based ART in HIV-infected children 6 to 35 months of age. This study (P1104 s) enrolled P1060 children at 5-11 years of age and evaluated their neuropsychological performance over 2 years using the KABC-II, TOVA, BOT-2, and parent-reported BRIEF. Cohorts were compared using GEE least-squares means adjusted for site, child age and gender, and personal and social characteristics for child and caregiver. 611 (246 HIV+, 183 HEU, 182 HU) of the 615 enrolled at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda) were available for analysis. Mean age was 7.2 years, 48% ma...
Frontiers in Pediatrics, 2022
Background: The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1104s study evaluated neuropsychological outcomes over 96 weeks in children living with HIV (CLHIV) aged 5-11 years at 6 Sub-Saharan African sites to explore associations between HIV-illness related biomarkers and neuropsychological outcomes. Methods: Children living with HIV had participated in IMPAACT P1060, which compared efficacy of nevirapine versus lopinavir/ritonavir in children initiating ART at <3 years of age. At age 5-11, neuropsychological evaluations of KABC cognitive ability, TOVA attention-impulsivity and BOT-2 motor domains were assessed and repeated after 48 and 96 weeks. Clinical, antiretroviral therapy (ART) and laboratory (immunological and virological) parameters were used to predict neuropsychological outcomes using linear mixed-effects multivariable regression models, controlling for child and caregiver characteristics. Results: 246 CLHIV (45% male, mean age at initial neuropsychological evaluation 7.1 yrs [SD 1.2]) began ART at a median age 14.9 months (IQR 8.2, 25.2). Nadir CD4 percentage was 14.7% (IQR 11.0, 19.5); the median peak viral load (VL) was 750 000 copies/ml (IQR 366 000, 750 000) and 63% had ≥WHO stage 3 clinical disease; 164 (67%) were on lopinavir/ritonavir, 71 Frontiers in Pediatrics 01 frontiersin.org Fairlie et al. 10.3389/fped.2022.899002 (29%) were on nevirapine and 7 (3%) were on efavirenz. Other antiretrovirals were similar. Nevirapine at P1104s study start or later was associated with poorer neuropsychological scores across all domains except Global Executive Composite, even when controlling for nadir CD4 percent and time-varying HIV VL. Other predictors of poorer scores in KABC domains included low birth weight, WHO stage 4 disease and serious illness history and elevated VL was associated with worse BOT-2 scores. Conclusion: Children receiving nevirapine had poorer neuropsychological scores than those on lopinavir/ritonavir. Antiretroviral choice might adversely impact neuropsychological performance. In addition, low birth weight and markers of severe HIV disease: advanced WHO clinical HIV disease, history of serious illness and an elevated VL, were associated with lower neuropsychological scores.
African Multi-Site Two-Year Longitudinal Study of Neurocognition in HIV Infected/Affected Children
SSRN Electronic Journal, 2019
Background. Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods. We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child's age and sex, and selected personal/family control variables. Results. The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values < .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. Conclusions. Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.
The Pediatric Infectious Disease Journal, 2013
We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes. Methods: Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDSdefining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319). Results: At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intel-ligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist. Conclusions: In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.
HIV Medicine, 2021
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
Validity of Neuropsychological Testing in Young African Children Affected by HIV
Journal of Pediatric Infectious Diseases
Introduction Western-constructed neuropsychological tests have been used in low- and middle-income countries to assess the impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and other chronic illnesses. We explore using such instruments cross-culturally in a sub-Saharan African setting. Methods IMPAACT P1104S was a 2-year observational study performed at six clinical sites (South Africa—three sites, Malawi, Uganda, and Zimbabwe) to assess and compare neuropsychological outcomes in three cohorts of children between the ages of 5 and 11 years: HIV-infected (HIV), HIV-exposed but uninfected (HEU), and HIV unexposed and uninfected (HU). Descriptive statistics compared sociodemographic characteristics among children at sites. Instruments included the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) cognitive ability, Test of Variables of Attention (TOVA) attention/impulsivity, Bruininks–Oseretsky Test of Motor Proficiency, 2nd edition (BOT-...
Neurodevelopmental benefits of antiretroviral therapy in Ugandan children aged 0-6 years with HIV
Journal of acquired immune deficiency syndromes (1999), 2014
Insufficient data on neurodevelopmental benefits of antiretroviral therapy (ART) in children. Prospective study of 329 mothers and children aged 0-6 years to assess neurodevelopment. Results stratified by the maternal (M) and child (C) HIV status (MHIV⁻/CHIV⁻, MHIV⁺/CHIV⁻, and MHIV⁺/CHIV⁺). Gross Motor, Visual Reception, Fine Motor, Receptive, and Expressive Language scores were assessed by Mullen Scales of Early Learning. Global cognitive function was derived from an Early Learning Composite (ELC) score. Standardized weight and height for age z scores were constructed, and the lowest 15% cutoff defined disability. Generalized linear models were used to estimate prevalence rate ratios (PRR) adjusted for the child's age, weight, and height. In HIV-positive children, generalized linear models assessed the impact of ART initiation and duration on neurodevelopment. Compared with MHIV⁻/CHIV⁻ children, HIV-positive children were more likely to have global deficits in all measures of n...
Impact of HIV and Atiretroviral Therapy on Neurocognitive Outcomes Among School-Aged Children
Journal of acquired immune deficiency syndromes (1999), 2017
The impact of HIV infection and antiretroviral therapy (ART) on neurocognitive outcomes among children aged 7-14 years was assessed. We hypothesized that ART would ameliorate neurocognitive sequelae of HIV infection. HIV-positive and HIV-negative mother-child pairs from the Rakai Community Cohort Study and ART clinics in Rakai, Uganda, were followed prospectively for 4 years. Exposures were stratified as: perinatally HIV infected, perinatally HIV exposed but uninfected, and HIV unexposed and uninfected. The Kaufman Assessment Battery for Children assessed sequential and simultaneous processing, learning, planning, knowledge, and fluid crystalized index for overall functioning. Multivariable generalized linear models estimated adjusted prevalence rate ratios by age. Of the 370 mother-child pairs, 55% were HIV unexposed and uninfected, 7% were perinatally HIV exposed but uninfected, and 37.9% were perinatally HIV infected. Among HIV-infected children, longer duration of ART was associ...
2019
ABSTRACTApproximately 10% of youth in sub-Saharan Africa are infected with the Human Immunodeficiency Virus. In Zambia, it is estimated that over 72,000 children have HIV infection, and despite access to combination antiretroviral therapy, many will experience HIV-associated neurocognitive deficits (HAND) encompassing cognitive and psychiatric sequelae such as global intellectual delay, executive dysfunction, and depressed mood. However, little is known about the neurocognitive profile of such children, the long-term outcomes and impacts of HAND, or the predictors and risk factors for HAND-related impairment. We have initiated the first-ever prospective, longitudinal study of neurocognition in children with HIV-infection in Zambia. Our overarching study goals are to validate cognitive and psychiatric testing tools in children with HIV infection in Zambia, and to determine if inflammatory biomarkers and brain imaging can prospectively identify children at high risk of developing HAND...