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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023412-22
Application #
8258275
Study Section
Special Emphasis Panel (ZRG1-AARR-G (02))
Program Officer
Mofenson, Lynne M
Project Start
1987-09-30
Project End
2016-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
22
Fiscal Year
2012
Total Cost
$550,751
Indirect Cost
$122,524
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Lehman, Dara A; Wamalwa, Dalton C; McCoy, Connor O et al. (2012) Low-frequency nevirapine resistance at multiple sites may predict treatment failure in infants on nevirapine-based treatment. J Acquir Immune Defic Syndr 60:225-33
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