In contrast to the US and Europe, the pediatric HIV/AIDS epidemic in sub-Saharan Africa continues to expand. Perinatal HIV infection has a significant impact on brain development, and the achievement and maintenance of developmental milestones. Even though more than 80% of childhood HIV infections occur in Africa, the impact of HIV/AIDS on the health of African children remains poorly documented. No data exists on the impact of antiretroviral treatment on neurodevelopment in resource poor settings. The mechanisms of HIV neuroinvasion and neuropathogenesis over the course of infection remain largely unknown. Neurovirulent substrains may be responsible for the development of HIV-encephalopathy. The evolution of unique HIV lineages in the CNS has been shown to play a role in the development of HIV- associated dementia. No data are available on the potential role of HIV CNS compartmentalization in HIV encephalopathy in young children. We propose to conduct a prospective longitudinal community-based study to determine the first order (HIV exposure and infection) and second order (maternal AIDS and AIDS orphans) effects of the HIV epidemic on the neurodevelopment of young children in the Democratic Republic of Congo. We will also perform a cross- sectional characterization of HIV env compartmentalization in the CNS in HIV-infected infants (prior to initiating ART) to test the hypothesis that unique HIV env lineages are present in CNS versus peripheral compartments, and to provide insight into the pathogenesis of HIV-associated CNS disease in young children. Finally, we will perform a longitudinal characterization of HIV env CNS compartmentalization in children whose CNS manifestations do not reverse following ART. A better understanding of how HIV impacts neurodevelopment and causes encephalopathy in children would ultimately aid in the development of therapeutic strategies to prevent neurological complications experienced by children and adults alike.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-ICP2-B (50))
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Mofenson, Lynne M
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University of North Carolina Chapel Hill
Public Health & Prev Medicine
Schools of Public Health
Chapel Hill
United States
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Sheahan, Anna; Feinstein, Lydia; Dube, Queen et al. (2017) Early Antiretroviral Therapy Initiation and Mortality Among Infants Diagnosed With HIV in the First 12 Weeks of Life: Experiences From Kinshasa, DR Congo and Blantyre, Malawi. Pediatr Infect Dis J 36:654-658
Smith, Emily R; Sheahan, Anna D; Heyderman, Robert S et al. (2017) Performance of HIV Rapid Tests Among Breastfeeding, Malawian Infants. Pediatr Infect Dis J 36:405-411
Smith, Emily R; Hudgens, Michael; Sheahan, Anna D et al. (2017) Timing of HIV Seroreversion Among HIV-Exposed, Breastfed Infants in Malawi: Type of HIV Rapid Test Matters. Matern Child Health J 21:248-252
Dara, Jasmeen; Dow, Anna; Cromwell, Elizabeth et al. (2015) Multivariable analysis to determine if HIV-1 Tat dicysteine motif is associated with neurodevelopmental delay in HIV-infected children in Malawi. Behav Brain Funct 11:38
Cromwell, Elizabeth A; Dow, Anna E; Low, Daniel et al. (2015) Barriers to successful early infant diagnosis of HIV infection at primary care level in Malawi. Pediatr Infect Dis J 34:273-5
Dow, Anna; Dube, Queen; Pence, Brian W et al. (2014) Postpartum depression and HIV infection among women in Malawi. J Acquir Immune Defic Syndr 65:359-65
Cromwell, Elizabeth A; Dube, Queen; Cole, Stephen R et al. (2014) Validity of US norms for the Bayley Scales of Infant Development-III in Malawian children. Eur J Paediatr Neurol 18:223-30
Hanrahan, Colleen F; Westreich, Daniel; Van Rie, Annelies (2012) Verification bias in a diagnostic accuracy study of symptom screening for tuberculosis in HIV-infected pregnant women. Clin Infect Dis 54:1377-8; author reply 1378-9
Sturdevant, Christa Buckheit; Dow, Anna; Jabara, Cassandra B et al. (2012) Central nervous system compartmentalization of HIV-1 subtype C variants early and late in infection in young children. PLoS Pathog 8:e1003094
Dube, Queen; Dow, Anna; Chirambo, Chawanangwa et al. (2012) Implementing early infant diagnosis of HIV infection at the primary care level: experiences and challenges in Malawi. Bull World Health Organ 90:699-704

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