September 2018 DAIDS Council-Approved Concepts

Concepts represent early planning stages for program announcements, requests for applications, or solicitations for Council's input. If NIAID publishes an initiative from one of these concepts, we link to it below. To find initiatives, go to Opportunities & Announcements.

NB: Council approval does not guarantee that a concept will become an initiative.

Table of Contents

Long-Acting Drug Delivery Systems for ART Optimization in HIV-1 Infected Children

Request for Applications—proposed FY 2020 initiative

Contact: Patrick Jean-Philippe

Objective: This initiative is intended to accelerate preclinical development of novel, safe, and effective long-acting drug delivery systems (LA-DDS) for improved, simplified treatment of HIV-1 in children. This initiative will target researchers engaged in developing existing LA-DDS platforms at early product development stages and will support specific preclinical activities to enable product optimization and accelerated translation to HIV-1 infected children.

Description: This funding opportunity announcement (FOA) will use a two-phase funding mechanism and negotiated milestones to determine transition to the second phase. The initial R61 phase will fund activities to optimize LA-DDS, including formulation optimization for preclinical pediatric studies. The R33 phase will fund preclinical activities [pharmacokinetic/pharmacodynamic (PK/PD) studies, anatomical tissue drug levels determination, antiviral efficacy] of the optimized LA-DDS formulation in a SHIV-/SIV-infected nonhuman primate (NHP) animal model or other suitable preclinical models aimed at generating data to facilitate rapid clinical translation and initiation of Phase I trials in children.

The scope of the research under consideration should meet the following desired optimal properties:

  • Proposal must build on existing work on the proposed LA-DDS, e.g., for an adult indication. The proposed LA-DDS may be in preclinical testing or early human clinical testing phase (up to Phase II) in adults but should not have undergone any clinical testing or have imminent plans for such testing in pediatric populations for anti-HIV-1 indications
  • A proposed LA-DDS with:
    • Incorporation and simultaneous delivery of a fully active antiretroviral combination
    • Minimum dosing interval of > 4 weeks
  • Target pediatric age groups: infants (0 to < 2 years), young children (2 to < 6 years), older children (6 to < 12 years), and adolescents (12 to < 18 years)
  • Administration strategies such as oral, implant (non-biodegradable or biodegradable), transdermal (continuous use or short exposure depot-forming), injectables, and other depot and non-depot forming systems nanoformulated or enabled through other engineering systems
  • Antiviral efficacy and safety of the proposed products within the LA-DDS in animal models, including antiviral efficacy study of the LA-DDS candidate in the R33 phase in NHPs. Animal models should be appropriate (age and maturation) for the chosen target population.
  • Characterization of the LA-DDS PK/PD properties including duration of use, PK tail, forgiveness, and lag period
  • Industry partnership and collaboration
  • Strongly encouraged:
    • Enhanced targeting of anatomical compartments (secondary lymphoid tissue, gut-associated lymphoid tissue, central nervous system)
    • Early assessment of preferred user characteristics in end user population, using established behavioral and social science tools
    • ​​​Target Product Profile identifying product optimal and minimally acceptable criteria

The following activities are nonresponsive and will not be reviewed:

  • De novo DDS/small molecule discovery work
  • Current Good Manufacturing Practices manufacture activities
  • Developing LA-DDS with durations of action that do not meet the minimum durations defined in the FOA
  • Intravenous infusion of any component of the LA-DDS
  • Use of any live biotherapeutic or vector system (e.g., viral, bacterial, fungal) to produce/deliver the anti-HIV component of the proposed drug product
  • Developing broadly neutralizing antibodies
  • LA-DDS platforms that are in late phases of clinical testing or planned clinical testing in pediatric populations
  • Working without an industry partner

Advancing Biomarker Discovery and Novel Point-of-Care Diagnostics for Active TB Disease Detection in HIV-1 Infected and Exposed Children

Request for Applications—proposed FY 2020 initiative

Contact: Patrick Jean-Philippe

Objective: To advance non-sputum-based tuberculosis (TB) diagnostics in HIV-1 infected and exposed uninfected children by promoting discovery and validation of novel TB biomarkers or development/optimization and early validation of novel TB diagnostic technologies for improved, simplified, rapid, and decentralized diagnosis of TB disease in these populations.

Description: The following activities are considered responsive:

  • Those aimed at new biomarker discovery on non-sputum-based matrices and early evaluation of their performance characteristics in well-characterized cohorts or bio-banked samples for detection of TB disease in children
  • Biomarker discovery activities are expected to include, but not be limited to:
    • Host RNA transcript expression profile, proteomics (hosts or pathogen derived)
    • Metabolomics
    • Mycobacterium tuberculosis (Mtb)-specific antibody functional profiling (FcR binding, effector function, glycosylation pattern)
    • Immune cells profiling
    • Other biomarkers (e.g., extracellular vesicles/exosomes)
    • Discovery activities involving more than one biomarker type are highly encouraged
  • Development/optimization and early evaluation of novel ultrasensitive detection tools for novel or existing Mtb or host response-based biomarkers
  • Evaluation of discriminatory ability along the spectrum of TB disease (microbiologically confirmed TB, clinically-diagnosed TB, latent/incipient TB) and not TB, including, when feasible, potentially confounding conditions (receipt vs. non-receipt of Bacillus Calmette-Guérin, non-tuberculous mycobacteria, pneumonia, and other respiratory diseases) is encouraged
  • Eligible matrices include serum, urine, stools, or other non-sputum matrices (e.g., exhaled air)
  • Target populations/age groups are HIV-infected or -exposed young children less than five years with diagnostic evaluation for TB disease in established prospective cohorts or well characterized stored samples from such cohorts
  • Proposed biomarker/diagnostic technologies that can be developed as point-of-care tools

Industry partnership is encouraged.

The following are nonresponsive and will not be reviewed:

  • Evaluation of sputum or other respiratory sample-based (e.g., gastric, nasopharyngeal aspirates) biomarkers or tests including molecular or microbiologic/culture-based tests
  • Initiation of late-phase prospective evaluation of new TB diagnostics in children (i.e., large studies powered to provide evidence of diagnostic accuracy for the assay). However, such studies, if already existing, can be used as a source of samples.
  • Validation of tests already approved/endorsed for use in that population (e.g., Xpert Ultra, urine lipoarabinomannan)
  • Cohorts/samples that do not include HIV-infected children and children less than five years

HIV/HBV Co-Infection: Research To Advance HBV Cure

Program Announcement With Set-Aside Funds—proposed FY 2020 initiative

Contact: Chris Lambros

Objective: Conduct clinical, basic, and translational research to identify and address the challenges to achieve hepatitis B virus (HBV) cure.

Description: The funding opportunity announcement will invite applications supporting research critical to developing cure strategies for HBV. Research areas to be supported by this program announcement with set-aside funds include but are not limited to:

  • Investigating how to stimulate HBV-specific innate immune response
  • Investigating how to restore HBV-specific adaptive immune response
  • Exploring basic mechanisms of HBV replication or HBV protein expression
  • Elucidating the mechanisms responsible for covalently closed circular DNA (cccDNA) biogenesis, homeostasis, and decay
  • Exploring the influence of the host on the HBV life-cycle
  • Developing efficient cell culture models to enhance viral spread
  • Identifying new viral targets and strategies to prevent drug resistance
  • Developing reproducible cell-free test systems for high-throughput antiviral screening
  • Developing small animal models that resemble infection in humans
  • Identifying therapeutics with the potential to permanently silence or eliminate cccDNA
  • Identifying biomarkers and diagnostic tools with good prognostic value to enable easy translation into clinical care
  • Developing more reliable noninvasive clinical tools for assessing liver injury and stage of infection

Novel RNAs in Virology (Including HIV) and Immune Regulation: Basic Science and Therapeutic Discovery

Program Announcement—proposed FY 2020 initiative

Contact: Lillian Kuo

Objective: The scientific objective is to support innovative basic research aimed at discovering and characterizing novel biologically active viral and/or host RNAs involved in virology (including HIV biology) and immune regulation. The program will also support discovery of novel functions of previously identified viral or host RNAs. These objectives include investigating the utility of these novel cellular or viral RNAs as drug targets through proof-of-concept studies.

Recent advances in RNA sequencing technologies have revealed a myriad of novel biologically active RNA species (e.g., lncRNAs, vaultRNAs, circRNAs, snoRNAs, piRNAs, rRNAs, YRNAs, tRNA fragments, and many others). In addition to intracellular activity, these novel RNA species may also have functional activity in the extracellular milieu where these extracellular RNAs (exRNAs) are selectively packaged into extracellular vesicles (exosomes) and/or bound to RNA-binding proteins or lipids.

These novel RNA species are hypothesized to have multiple functional roles and biological activities in basic biochemistry, molecular virology, cell biology, and regulating both innate and adaptive immune responses. Leveraging innovative basic RNA biology will ultimately open new opportunities for discovering or designing novel therapeutic interventions. The scientific objectives are to 1) support basic research on novel RNA species or novel functions of known RNAs, regulating viral infection or innate and/or adaptive immune pathways and 2) enable exploratory studies for identifying novel viral or cellular RNA targets for the discovery or design of interventions.

Description: This initiative will support exploratory research ranging from early RNA discovery and fundamental RNA biochemistry extending to the discovery or design of interventions. The focus is on novel viral and/or host cellular RNA species or new biological activities of previously identified RNAs with regulatory functions or biological activity in virology, host cell biology, innate and adaptive immune signaling pathways, immune regulation, and/or immunopathogenesis.

The initiative will support high-risk, high-reward, exploratory, and innovative research that may include but is not limited to:

  • Basic research on the fundamental mechanisms of novel viral and/or host intra- or extracellular RNAs in regulating virus replication, immunopathogenesis, infection-associated expression patterns, virus latency, and/or persistence
  • Basic research in defining either roles of novel RNAs or novel functions of known RNAs in regulating innate or adaptive immunity and inflammation
  • Structural biology of novel RNAs in viral infections and immunity
  • Discovery and validation of the potential utility of novel RNAs as biomarkers
  • Therapeutic approaches using or targeting novel RNAs
  • Developing novel RNA inhibitors and mimics as therapeutic targets
Content last reviewed on October 3, 2018