Michael J Boivin1, Linda Barlow-Mosha2, Miriam C Chernoff3, Barbara Laughton4, Bonnie Zimmer5, Celeste Joyce6, Mutsa Bwakura-Dangarembizi7, Mmule Ratswana8, Nasreen Abrahams9, Lee Fairlie8, Hermien Gous8, Portia Kamthunzi10, Katie McCarthy11, Itziar Familiar-Lopez1, Patrick Jean-Phillippe12, Joan Coetzee4, Avy Violari6, Mark F Cotton4, Paul E Palumbo13. 1. Departments of Psychiatry and Neurology & Ophthalmology, Michigan State University, East Lansing, Michigan, USA. 2. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda. 3. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA. 4. Family Clinical Research Unit, Tygerberg Hospital, Department of Pediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa. 5. Frontier Science and Technology Research Center, Amherst, New York, USA. 6. Perinatal HIV Research Unit (PHRU), Chris Hani Baragwanath Hospital, University of Witwatersrand, Johannesburg, South Africa. 7. Harare Family Care CRS, Parirenyatwa Hospital, University of Zimbabwe, Harare, Zimbabwe. 8. Wits Reproductive Health and HIV Institute (Wits RHI), Shandukani Research Centre CRS, University of the Witwatersrand. 9. Soweto IMPAACT CRS, Perinatal HIV Research Unit (PHRU), Chris Hani Baragwanath Hospital, Johannesburg, South Africa. 10. University of North Carolina (UNC) Project, Tidziwe Centre, Kamuzu Central Hospital, Lilongwe, Malawi. 11. Clinical Research Management, FHI360, Durham, North Carolina. 12. Maternal, Adolescent, & Pediatric Research Branch (MAPRB), Division of AIDS, NIH/NIAID, Bethesda, Maryland. 13. Division of Infectious Diseases and International Health, Hitchcock Medical School of Dartmouth University, Lebanon, New Hampshire, USA.
Abstract
OBJECTIVE AND DESIGN: Children with HIV infection (HIV+) are at neuropsychological risk, but few studies have evaluated this at multiple sites in low-income and middle-income countries. We compared neuropsychological outcomes at enrollment (>5 years age) among HIV+, HIV perinatally exposed uninfected (HEU), and HIV unexposed uninfected (HUU) children from four sub-Saharan countries. METHODS: IMPAACT P1060 compared nevirapine versus lopinavir/ritonavir-based antiretroviral treatment (ART) in HIV-infected children 6-35 months of age. The present study (P1104s) enrolled P1060 children at 5-11 years of age and evaluated their neuropsychological performance over 2 years using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), Tests of Variables of Attention (TOVA), Bruininks-Oseretsky Test, 2nd edition (BOT-2), and parent-reported Behavior Rating Inventory of Executive Function (BRIEF). Cohorts were compared using generalized estimating equations least-squares means adjusted for site, child age and sex, and personal and social characteristics for child and caregiver. RESULTS: Six hundred and eleven (246 HIV+, 183 HEU, 182 HUU) of the 615 enrolled at six sites [South Africa (three), Zimbabwe, Malawi, Uganda] were available for analysis. Mean age was 7.2 years, 48% male, 69% in school. Unadjusted and adjusted comparisons were consistent. HIV+ children performed significantly worse than HEU and HUU cohorts on all KABC-II cognitive performance domains and on BOT-2 total motor proficiency (P < 0.001), but not on the BRIEF Global Executive Indices. HUU and HEU cohorts were comparable on cognitive outcomes. HIV+ children initiated on ART before 1 year of age had significantly better BRIEF evaluations (lower scores - fewer behavior problems), compared with those started after (P = 0.03). CONCLUSION: Significant cognitive deficits were documented among HIV+ children at school age, even when started on ART at an early age. Earlier HIV treatment, neuropsychological monitoring, and rehabilitative interventions are all needed. Subsequent testing for 2 more years will help further evaluate how HIV infection and exposure affect the developmental trajectory.
OBJECTIVE AND DESIGN:Children with HIV infection (HIV+) are at neuropsychological risk, but few studies have evaluated this at multiple sites in low-income and middle-income countries. We compared neuropsychological outcomes at enrollment (>5 years age) among HIV+, HIV perinatally exposed uninfected (HEU), and HIV unexposed uninfected (HUU) children from four sub-Saharan countries. METHODS: IMPAACT P1060 compared nevirapine versus lopinavir/ritonavir-based antiretroviral treatment (ART) in HIV-infectedchildren 6-35 months of age. The present study (P1104s) enrolled P1060 children at 5-11 years of age and evaluated their neuropsychological performance over 2 years using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), Tests of Variables of Attention (TOVA), Bruininks-Oseretsky Test, 2nd edition (BOT-2), and parent-reported Behavior Rating Inventory of Executive Function (BRIEF). Cohorts were compared using generalized estimating equations least-squares means adjusted for site, child age and sex, and personal and social characteristics for child and caregiver. RESULTS: Six hundred and eleven (246 HIV+, 183 HEU, 182 HUU) of the 615 enrolled at six sites [South Africa (three), Zimbabwe, Malawi, Uganda] were available for analysis. Mean age was 7.2 years, 48% male, 69% in school. Unadjusted and adjusted comparisons were consistent. HIV+ children performed significantly worse than HEU and HUU cohorts on all KABC-II cognitive performance domains and on BOT-2 total motor proficiency (P < 0.001), but not on the BRIEF Global Executive Indices. HUU and HEU cohorts were comparable on cognitive outcomes. HIV+ children initiated on ART before 1 year of age had significantly better BRIEF evaluations (lower scores - fewer behavior problems), compared with those started after (P = 0.03). CONCLUSION: Significant cognitive deficits were documented among HIV+ children at school age, even when started on ART at an early age. Earlier HIV treatment, neuropsychological monitoring, and rehabilitative interventions are all needed. Subsequent testing for 2 more years will help further evaluate how HIV infection and exposure affect the developmental trajectory.
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