Michael J Boivin1,2,3, Miriam Chernoff4, Lee Fairlie5, Barbara Laughton6, Bonnie Zimmer7, Celeste Joyce8, Linda Barlow-Mosha9, Mutsawashe Bwakura-Dangarembizi10, Tichaona Vhembo10, Mmule Ratswana5, Portia Kamthunzi11, Katie McCarthy12, Itziar Familiar-Lopez1, Patrick Jean-Philippe13, Joan Coetzee6, Nasreen Abrahams8, Hermien Gous5, Avy Violari8, Mark F Cotton6, Paul E Palumbo14. 1. Department of Psychiatry, Michigan State University, East Lansing, Michigan, USA. 2. Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan, USA. 3. Department of Psychiatry, the University of Michigan, Ann Arbor, Michigan, USA. 4. Center for Biostatistics in Acquired Immunodeficiency Syndrome Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. 5. Wits Reproductive Health and Human Immunodeficiency Virus Research Centre, Shandukani Clinic, Johannesburg, South Africa. 6. Family Centre for Research with UBUNTU, Department of Paediatrics and Child Health, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa. 7. Frontier Science Foundation, Amherst, New York, USA. 8. Perinatal Human Immunodeficiency Virus Research Unit, University of the Witwatersrand, Johannesburg, South Africa. 9. Makerere University-Johns Hopkins University Research Collaboration CRS, Kampala, Uganda. 10. Harare Family Care CRS, University of Zimbabwe, College of Health Sciences Clinical Trials Unit, Harare, Zimbabwe. 11. University of North Carolina Project-Lilongwe, Malawi CRS, Lilongwe, Malawi. 12. Clinical Research Management, FHI360, Durham, North Carolina, USA. 13. National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, Maryland, USA. 14. Hitchcock Medical School of Dartmouth University, New Lebanon, New Hampshire, USA.
Abstract
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.
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.
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