Concepts for proposed Requests for Applications (RFA) are reviewed during the Open Session of Council. These are the features of the process:

• A brief concept description, written by the program staff proposing a grant solicitation, is posted on the Council website.
  
  
• Dr. Alexander will present the concepts during the Open Session. Program staff will be available to answer questions if called upon but, in general, will not participate in the presentation.
  
  
• Following brief presentation and discussion, Council members will be asked to indicate their opinion of each concept.
  
  
• Comments, suggestions, and Council advice will be recorded by NICHD staff.

This approach to concept review:

• Meets the NIH requirement for public presentation of concepts and the opportunity for public comment.
  
  
• Provides a wide spectrum of expertise for the consideration of concepts, including scientific, policy, and advocacy perspectives. The process should encourage the presentation and evaluation of broad concepts, without detailed or in-depth discussion of the specific science. Such discussion, typical when concepts are reviewed by a group with more narrowly focused expertise, goes well beyond the purpose of this review. Indeed, it places those involved in a potential conflict of interest situation that would prevent them from responding to a resultant RFA should they choose to do so.
  
  
• Enables the full Council to consider individual initiatives within the broader context of many planned initiatives, giving us the benefit of multiple perspectives in the overall planning of an NICHD research agenda.
  

For this meeting, one concept was reviewed:

Pediatric HIV-AIDS Cohort Study (PHACS)

Pediatric HIV-AIDS Cohort Study (PHACS)

January 2009

A Request for Applications is proposed using the U01 mechanism to continue the “Pediatric HIV-AIDS Cohort Study (PHACS).” This initiative is currently co-funded by NIAID, NIDA, NIMH, NHLBI, and NIDCD, all of which are expected to continue; NINDS plans to co-fund in 2010. Competition will be limited to applicant institutions that were funded in the initial competitive segment, in order to efficiently and seamlessly maintain PHACS activities.

Purpose
The proposed RFA is a competing renewal, using the U01 mechanism, to provide support for continuing the observational cohorts developed during the first competitive funding cycle. These cohorts address two critical issues in HIV research: the long-term safety of in utero exposure to multiple antiretroviral drugs in HIV-exposed but uninfected children, and the interactive effects of HIV and its treatments on perinatally infected children and adolescents.

Scope
PHACS includes 2 distinct cohorts – 1) HIV-exposed but uninfected infants and children and 2) HIV-infected children and adolescents. The study of an open cohort of HIV-uninfected children exposed to antiretrovirals during pregnancy and early infancy to identify potential consequences continues to be a critical need as new drugs and more complex antiretroviral regimens are increasingly being used by HIV-infected pregnant women to prevent mother to child transmission and/or for treatment for maternal health reasons. Continuation of this effort will allow for ongoing evaluations of new antiretroviral exposures in the HIV-uninfected cohort in utero and postnatally and further work to identify specific adverse events and potential etiologic factors. Over 1,300 HIV-exposed uninfected children have been enrolled in PHACS to date and are under active follow-up.

Perinatally-infected youth now routinely survive to adulthood but face the consequences of prolonged HIV infection and long-term antiretroviral therapy on multiple organs and systems in the body. Given the great increase in the number of available antiretrovirals but the limited data on the long term safety of these agents in growing and developing youth, a cohort study such as this also continues to have critical importance. Over 300 children and adolescents with perinatal HIV infection and nearly 100 uninfected control subjects have been enrolled and are under intensive evaluation in PHACS to date; a high prevalence of abnormalities has already been detected (for example, 47% of the HIV-infected cohort have been found to have hyperlipidemia).

Since this initiative represents the extension of funding for an established set of cohorts, Program expects that competition will be limited to applicant institutions that were funded in the initial competitive segment. Awards made to new institutions would not serve the interests of efficiently and seamlessly maintaining PHACS activities.

Objectives
The goals of the PHACS network: (1) Acquire more definitive information regarding long-term safety of antiretroviral drugs used during pregnancy and in infancy on HIV-exposed but uninfected children, and to estimate the upper bounds of risk to children associated with in utero exposure to antiretroviral drugs and (2) Understand the effect of HIV and its treatment on various domains including cardiovascular risk, bone health, sexual maturation, pubertal development, and mental health, in perinatally HIV-infected children and adolescents.

Program Contact
Rohan Hazra, MD
Medical Officer
Pediatric, Adolescent and Maternal AIDS Branch
Center for Research for Mothers and Children