Robert Paul1, Tanakorn Apornpong2, Wasana Prasitsuebsai2, Thanyawee Puthanakit2,3, Vonthanak Saphonn4, Linda Aurpibul5, Pope Kosalaraksa6, Suparat Kanjanavanit7, Wicharn Luesomboon8, Chaiwat Ngampiyaskul9, Tulathip Suwanlerk10, Kea Chettra11, William T Shearer12, Victor Valcour13, Jintanat Ananworanich2,14,15, Stephen Kerr2,16. 1. Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, MO. 2. HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand. 3. Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 4. University of Health Sciences, Phnom Penh, Cambodia. 5. RIHES, Chiang Mai University, Chiang Mai, Thailand. 6. Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 7. Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand. 8. Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand. 9. Nakornping Hospital, Chiang Mai, Thailand. 10. Prapokklao Hospital, Chantaburi, Thailand. 11. Social Health Clinic, Phnom Penh, Cambodia. 12. Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 13. Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA. 14. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD. 15. Department of Global Health, Academic Medical Center, The University of Amsterdam, Amsterdam, the Netherlands. 16. The Kirby Institute, University of New South Wales, Sydney, Australia.
Abstract
BACKGROUND: HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown. METHODS: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models. RESULTS: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups. CONCLUSIONS: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.
BACKGROUND:HIV-infectedchildren with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown. METHODS: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models. RESULTS: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups. CONCLUSIONS: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.
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