Virologic determinants of very early antiretroviral treatment responses of infants with in utero HIV-1
Active Project Grant Awarded Last action
- Award ID
- R21HD118590
- Recipient
-
The Johns Hopkins University UEI FTMTDMBR29C7
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $426,719
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date 78% complete
- Place of performance
- Baltimore, MD 21205, USA
Award details come from USAspending.gov.
Description
- Abstract
- Initiation of very early antiretroviral therapy (art) in neonates with in utero HIV-1 leads to the possibility of long-term art-free control in a small subset of neonates. In the impaact P1115 clinical trial, very early art has led to four cases of long-term, art- free control in children. In addition to this outcome, SEX differences were observed with respect to plasma viral load, cell-associated HIV-1 DNA concentrations, and the ability to maintain sustained virologic suppression. These observations are consistent with previously published research in other cohorts that revealed SEX differences in HIV-1 replication capacity and interferon resistance with respect to in utero HIV-1 transmission. To further interrogate the virologic determinants that lead to the formation of the viral reservoir, we propose to create infectious molecular clones from the GAG-pro and ENV regions of the near full-length single genome sequences from the proviral HIV- 1 DNA of impaact P1115 participants. These recombinant viruses will be assayed for replication capacity and interferon resistance, which will be examined against early life biomarkers of in utero HIV-1 transmission such as plasma viral load, HIV-1 DNA concentrations, and biological SEX. In addition to employing the conventional TZM-BL and CEM-GXR-25 immortalized cell lines to determine viral infectivity and replication capacity, we propose to also compare HIV-1 interferon resistance in primary CD4+ cells isolated from adult males and females or cord blood cells to also investigate the role of target cell type on interferon resistance. Altogether, these studies will fill a critical GAP in our understanding of retroviral infection in fetal cells and by biological SEX and their implication for sustained virologic control in postnatal life.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $194,219 | |
| Original award | $232,500 |
Quick answers
Who received award R21HD118590?
R21HD118590 was awarded to The Johns Hopkins University by National Institute of Child Health and Human Development (National Institutes of Health) on April 16, 2025.
How much is award R21HD118590 worth?
$426,719 has been obligated on R21HD118590.
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