In the regions most affected by the HIV-1 epidemic, the majority of children with HIV-1 remain undiagnosed until they experience an acute co-infection. For these children, the best time to initiate ART is not known. Urgent ART may be associated with increased side-effects, difficulty in administration and increased immune reconstitution inflammatory syndrome (IRIS), but these risks may be outweighed by prompt decrease in viral replication, faster immune recovery and better control of both HIV-1 and the concomitant infection. We propose to conduct a randomized clinical trial to determine the potential benefit of highly accelerated ART in children who are diagnosed with HIV-1 at the time of hospitalization. Hospitalized children newly diagnosed with HIV-1 infection will be randomized to receive either emergent ART (within 48 hours) or post-stabilization ART (within 2 weeks). Survival will be the primary outcome of interest and we will nest immunologic studies to define predictors of survival and IRIS. This trial will address questions of critical importance to children with HIV-1 and will result in a strong epidemiologic framework for molecular studies on pediatric HIV-1 pathogenesis and IRIS. Concurrent with the trial we will explore measures to prevent late pediatric HIV-1 diagnosis by developing models for home-based diagnosis of asymptomatic HIV-1 infected children and to provide a comparison cohort of HIV-1 infected children without severe infection.

Public Health Relevance

In resource-poor settings, many children are first diagnosed with HIV-1 infection while hospitalized for a severe infection. Mortality is very high in these children, and it is possible that rapid initiation of antiretroviral therapy may improve prognosis. However, the potential benefits of early antiretroviral initiation must be weighed against the potential risks of increased drug toxicity or immune reconstitution inflammatory syndrome (IRIS). This study will utilize a randomized clinical trial design to compare rates of mortality and IRIS among hospitalized children newly diagnosed with HIV, who will be randomized to initiation of antiretroviral therapy during acute illness versus after stabilization of acute illness.

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-AARR-G (02))
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Mofenson, Lynne M
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University of Washington
Public Health & Prev Medicine
Schools of Medicine
United States
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Beima-Sofie, Kristin; Wamalwa, Dalton; Maleche-Obimbo, Elizabeth et al. (2018) Toll-like receptor 9 polymorphism is associated with increased Epstein-Barr virus and Cytomegalovirus acquisition in HIV-exposed infants. AIDS 32:267-270
Pankau, Mark D; Wamalwa, Dalton; Benki-Nugent, Sarah et al. (2018) Decay of HIV DNA in the Reservoir and the Impact of Short Treatment Interruption in Kenyan Infants. Open Forum Infect Dis 5:ofx268
Gómez, Laurén A; Crowell, Claudia S; Njuguna, Irene et al. (2018) Improved Neurodevelopment After Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus-infected Children. Pediatr Infect Dis J 37:916-922
LaCourse, Sylvia M; Pavlinac, Patricia B; Cranmer, Lisa M et al. (2018) Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children. AIDS 32:69-78
Wagner, Anjuli D; O?Malley, Gabrielle; Firdawsi, Olivia et al. (2018) Brief Report: Disclosure, Consent, Opportunity Costs, and Inaccurate Risk Assessment Deter Pediatric HIV Testing: A Mixed-Methods Study. J Acquir Immune Defic Syndr 77:393-399
LaCourse, Sylvia M; Cranmer, Lisa M; Njuguna, Irene N et al. (2018) Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human Immunodeficiency Virus-Infected Children. Clin Infect Dis 66:1798-1801
Njuguna, Irene N; Cranmer, Lisa M; Otieno, Vincent O et al. (2018) Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial. Lancet HIV 5:e12-e22
Suter, Megan K; Karr, Catherine J; John-Stewart, Grace C et al. (2018) Implications of Combined Exposure to Household Air Pollution and HIV on Neurocognition in Children. Int J Environ Res Public Health 15:
Wagner, Anjuli D; Njuguna, Irene N; Andere, Ruth A et al. (2017) Infant/child rapid serology tests fail to reliably assess HIV exposure among sick hospitalized infants. AIDS 31:F1-F7
Benki-Nugent, Sarah; Wamalwa, Dalton; Langat, Agnes et al. (2017) Comparison of developmental milestone attainment in early treated HIV-infected infants versus HIV-unexposed infants: a prospective cohort study. BMC Pediatr 17:24

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