A request for applications (RFA) with set aside is proposed, entitled “Evaluation of the Latent HIV Reservoir in HIV-Infected Infants and Children with Early Antiretroviral Treatment and Virologic Control” using the R01 Research Project grant mechanism.
The purpose of this RFA is to stimulate research to investigate the latent HIV reservoir in children, as this area of research has focused on adults and there have been few pediatric studies.
Applicants should propose novel methods for evaluating the latent reservoir and factors associated with such reservoir in children with perinatal HIV infection who had early treatment and continuous viral suppression. Areas of interest include, but are not limited to:
- Evaluate whether early ART in children affects proviral reservoir size, immune activation, and level of persistent viremia;
- Conduct studies to identify and quantify the tissues and cell types that constitute the persistent viral reservoir in children receiving early ART;
- Develop tools to measure and quantify HIV in reservoirs such as novel imaging techniques;
- Investigate the role of immune activation, inflammation, and their mediators in various tissues on HIV persistence in infants with perinatal HIV infection;
- Evaluate whether duration of viral suppression after ART is associated with viral reservoir size, ongoing viremia, immune activation, and HIV-specific immune responses in HIV-infected children;
- Identify and validate viral and host cellular factors and functions involved in the persistence of HIV infection despite ART that could be targeted for eradication of persistent virus in HIV-infected children;
- Delineate the viral, host, and immune mechanisms involved in the persistence of HIV infection despite effective antiretroviral therapy (ART), and the establishment and maintenance of the latent viral reservoir.
The goal is to provide data to evaluate latent viral pools in children who received therapy in the early months of life and have survived with undetectable plasma viremia. It is possible that children initiating effective ART at ≤ 6 months of age are more likely to have limited HIV reservoirs, decreased immune activation, absent residual viremia and diminished HIV-specific antibody responses compared to those treated after 6 months. ART in these infants leads to a unique state of viral persistence whereby control of HIV replication is solely from ART effects as most of these children have little to no HIV-specific cellular immunity. This population of early-treated children presents a unique opportunity to study this extraordinary state of virus-host interaction arising from early ART. Identification of a composite virologic and immunologic biomarker profile in this population will provide quantitative insights into HIV persistence not under immune control that help define mechanisms of HIV persistence, and aid with designing and assessing therapeutic strategies aimed at achieving functional cure for this population. AMFAR has identified research on the evaluation of the latent HIV reservoir in children with very early ART therapy to determine whether there is cure to be an area of highest priority.
Lynne M. Mofenson MD
Maternal and Pediatric Infectious Disease Branch
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