May
2009 DAIDS Council-Approved Concepts
NB: Concepts represent early planning stages for PAs, RFAs, or solicitations for Council 's input. Council approval does not guarantee that a concept will become an initiative.
If NIAID publishes an initiative from one of these concepts, we link to it below. For a full list of initiatives, go to NIH Funding Opportunities Relevant to NIAID.
Table of Contents
Integrated Preclinical/Clinical Program for Topical Microbicides
Request for Applications
Contact: Jim Turpin
Phone: 301-451-2732
Internet: jturpin@niaid.nih.gov
Objective:
- Stimulation of a strong and diverse base in preclinical discovery and development of novel single microbicides, combination microbicides, and microbicide strategies for vaginal, rectal, and/or penile use.
- Support for translation of novel microbicides and microbicide strategies from preclinical studies to pre-Phase I clinical trials.
- Facilitation of entry of new methods and expertise into microbicide development such as:
- Integration of behavioral research into the early stages of microbicide development.
- Modulation of innate and adaptive vaginal defenses in order to promote microbicide use that is associated with coitus.
- Validation of models and surrogate markers for safety, efficacy, and acceptability.
Description: This initiative will support the board range of research necessary to advance well-characterized microbicide leads and strategies into clinical studies. Specific types of supportable research include: (1) development of new single or combination microbicides for vaginal, rectal, and penile use; (2) identification and validation of new microbicide targets and strategies; (3) integration of microbicides with other prevention strategies; (4) development of new and optimization of existing delivery methods with the aim of creating long lasting, minimal dosing, coital disassociated microbicides; (5) exploration of the relationship between behavioral and social factors affecting adherence and acceptability and the biophysical properties of formulated microbicides; and (6) pre-phase 1 trials to study the pharmacology, distribution, and effect of microbicides on the female reproductive and GI tract mucosa. The IPCP-HTM requires the participation of an industry partner, providing a mechanism for industry to participate in topical microbicide development with reduced risk.
The current IPCP-HTM will be updated to incorporate changes in the field (elimination of candidates, strategies, or over-represented areas of research in the DAIDS portfolio) occurring since its issuance. The RFA will also be modified so that various activities critical to candidate development such as basic/preclinical development, IND-enabling critical path studies (GLP toxicology and pharmacology, GMP manufacturing), animal model testing, behavioral and social studies, and pre-phase 1 clinical trials are offered in modules with specific RFA direct cost limitations and submission requirements (i.e., they must constitute projects). The modification will allow for maximum flexibility by investigators in assembling their multidisciplinary applications. Expanded funding for the program will allow awards that can incorporate all modules.
Next Generation PrEP
Request for Applications
Contact: Fulvia Veronese
Phone: 301-402-4148
Internet: veronesf@niaid.nih.gov
Objective: The objectives for this initiative are to:
- Strengthen and expand the pool of dedicated investigators to create a robust research portfolio for pre-exposure prophylaxis (PrEP) within DAIDS.
- Create a rational pipeline for the identification and discovery of the next generation of PrEP with prolonged activity and optimal tissue penetration.
- Develop a basic and preclinical algorithm to select and advance PrEP candidates to clinical studies.
Description:
- Development of a pipeline for second and subsequent generations of PrEP agents which, preferably, are not included in current antiretroviral treatment regimens.
- Discovery of agents with increased penetration of target tissue and prolonged half-life to maximize public health impact.
- Generation of comprehensive pK and pD data including intracellular levels in cervicovaginal, rectal, and penile mucosal tissue to determine the minimal effective prophylactic dose in animal models and humans.
- Systematic studies in animal models as a prelude to screening agents and selecting best candidates.
- Studies on selection of resistance.
- Development of long acting delivery systems that will provide for long-term protection and infrequent dosing.
- Comprehensive preclinical safety studies that address the long-term use of PrEP regimens.
Understanding HIV Persistence
Request for Applications
Contact: Sandra Bridges
Phone: 301-496-8198
Internet: sbridges@niaid.nih.gov
Objective: The ultimate goal is the eradication of HIV-1 in infected subjects, i.e., a cure for HIV infection. This initiative addresses the final obstacle to that goal - purging reservoirs of HIV infection that remain despite optimal antiretroviral therapy (ART).
Scientific objectives are:
- Better understanding of the basic biology of HIV reservoirs, both latent and persistently replicating, in order to understand why these reservoirs cannot be eradicated with current ART.
- Design and development of safe strategies for reducing or reversing latency.
Description: This initiative will support basic and clinical research in three areas:
- Basic research to identify and characterize the cellular reservoirs of HIV in HAART-treated individuals.
- Development of assays that are physiologically relevant and represent the spectrum of cell types that may harbor latent HIV or permit viral replication in the presence of potent antiretroviral treatment.
- High throughput screening of drug candidates; preclinical and (possibly) initial clinical testing of new agents/strategies.
International Epidemiologic Databases to Evaluate AIDS
Request for Applications
Contact: Carolyn Williams
Phone: 301-402-2305
Internet: cwilliams@niaid.nih.gov
Objective: International Epidemiologic Databases to Evaluate AIDS (IeDEA) investigators bring together HIV clinical and research datasets from world regions to answer key questions about the natural and treated history of HIV infection that can only be answered with large sample sizes. IeDEA validates and harmonizes these data. It develops novel statistical methods to account for missing data and understand and minimize bias and utilizes other techniques to maximize the utility of observational data. The goal is to conduct analyses that produce comparable results across regions and combine data from multiple regions to answer compelling questions.
Description: IeDEA II will enable continued competitive funding for five U.S. institutions and two European universities to conduct research in seven global regions of the world. The program supports epidemiologists, data management specialists, and statisticians to conduct research on collected clinical data. Sources include cohort studies, clinical trials networks, public and private clinics and hospitals, and private care providers. IeDEA provides training and support to clinical/research staff in country. This renewal also proposes to expand the consortium to include two new regional datacenters from Eastern Europe and Central Asia to expand data collection in currently funded regions and to support increased analytic capacity for the large datasets assembled by the currently funded regions.
Reagent Resource Support Program for AIDS Vaccine Development
Request for Proposals
Contact: Matthew Gormley
Phone: 301-451-3683
Internet: gormleym@niaid.nih.gov
Objective: This contract initiative will enable production and/or purchase of high-quality reagents and assays in support of preclinical AIDS vaccine research conducted by NIAID-supported investigators and NIAID partners in the AIDS vaccine field.
Description: The renewal contract will support (1) production of reagents and performance of assays in support of preclinical AIDS research and (2) the purchase of reagents and assays from other sources. The contractor will produce, synthesize, and purify critical reagents; purchase reagents and assays; perform standard quality control testing to guarantee the quality of reagents made in-house and obtained from outside sources; label and store reagents and specimens from animal studies; track (through a web-accessible inventory database) and ship reagents; and coordinate special reagent-dependent projects. The contractor will support multiple "end-users;" handle key reagents such as proteins for Env-based studies, DNA plasmids, and reagents for ad hoc assay support (e.g., ELISAs, ICS/flow cytometry, immunogenicity in rabbits, infectivity, microarrays); and store a diverse set of key samples. No substantial changes in scope, mechanism, and/or budget from previous solicitations are anticipated.
Mechanisms and Prevention of Sexual Transmission of HIV/SIV
Request for Applications
Contact: Geetha Bansal
Phone: 301-496-5042
Internet: gbansal@niaid.nih.gov
Objective: The broad scientific objective of this initiative is to fill research gaps in basic biology of sexual HIV transmission, vaccines, and non-vaccine preventive interventions, such as microbicides and pre-exposure prophylaxis (PrEP).
Specific objectives include:
- Exploring early events in host cell-virus interaction and transmission of HIV/SIV at mucosal sites.
- Understanding immune defense mechanisms and their regulation at mucosal surfaces.
- Defining the requirements for optimal induction of mucosal protection against HIV/SIV.
- Acquiring novel insight for identifying vaccines and non-vaccine biomedical prevention strategies to protect mucosal surfaces.
Description: The initiative will focus on understanding the mucosal route of HIV/SIV acquisition and cell-cell transmission. Very few funded projects examine very early transmission events in the tissue where it occurs. Elucidation of the mechanisms and factors involved in the early processes could identify novel approaches for preventing HIV infection in humans.
Examples of projects it will support include:
- Identifying novel viral or cellular targets that can be exploited for either vaccine or microbicide development.
- Identifying mucosal epithelial factors involved in barrier function and immune cell recruitment.
- Insight into the relationship between recruitment of activated immune cells and establishment of susceptible target cell pool.
- Understanding immunological and virological factors affecting duration of pre-integration latency.
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