January 2017 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

Fiscal Year 2018 Concepts

Fiscal Year 2018 Small Business Innovation Research (SBIR) Contract Solicitation Topic

Therapeutic Strategies for the Converging TB/T2DM/HIV Epidemics

Program Announcement—proposed FY 2018 initiative

Contact: Daniel Frank

Objective: 

  • Improved understanding on dysregulation of innate and adaptive immunity induced by type 2 diabetes mellitus (T2DM), Mycobacterium tuberculosis (Mtb), and HIV pathogenesis.
  • Collaborations between endocrinologists, immunologists, and infectious disease experts to improve understanding of T2DM/HIV/tuberculosis (TB) pathogenic interactions, including effects on immunometabolism and chronic inflammation.
  • Identification of targets and initial development of novel therapies to reverse immunosuppression and excess inflammation caused by T2DM and TB in the context of HIV infection.

Description: 

  • Elucidation of pathogenic mechanisms underlying the interactions among TB, T2DM (as well as pre-diabetes), and HIV, including their roles in immune dysregulation, and how these effects impact development, progression, and treatment outcomes.
  • Identification of specific targets to reverse immune dysregulation caused by T2DM/pre-DM and Mtb infection with and without HIV infection. 
  • Identification of promising and practical targeted therapeutic interventions to optimize treatment strategies for TB and T2DM in the context of HIV co-infection.
  • Development of cell lines, animal models, and recruitment of cohorts for human tissue samples to accomplish these goals.

HIV Drug Resistance: Genotype-Phenotype-Outcome Correlations

Program Announcement—proposed FY 2018 initiative

Contact: Keith Crawford

Objective: The objectives of this initiative are to provide data to better evaluate correlations between HIV drug resistance genotype, in vitro phenotype of the virus (i.e., drug susceptibility), and virologic outcome (i.e., virologic success or failure). Applications are sought in three specific areas:

  1. To better elucidate the role of minority variants in developing resistance to antiretroviral drugs and the effect of minor variants on virologic outcomes in both B and non-B subtypes. Standard genotypic resistance tests use Sanger sequencing to identify drug resistance mutations but can detect only mutations present at greater that 15 percent frequency of an individual’s quasispecies. Some studies suggest that mutations present at 1 percent or less may result in clinical treatment failure.
  2. To understand genotype-phenotype-outcome correlations in non-B subtypes. Non-B subtypes may have naturally-occurring polymorphisms that confer resistance to certain antiretrovirals. Resistance mutations may also have different effects (differences in fold-sensitivity to a drug) across subtypes. Some subtypes appear to display intrinsically reduced susceptibility to certain antiretroviral drugs, increasing the risk of failure. 
  3. To better understand why some non-nucleoside reverse transcriptase inhibitors maintain activity and help prevent virologic failure in protease inhibitor-based regimens, even in the presence of drug resistance mutations.

Description: Projects that will be supported include:

  • Studies focused on determining the biological basis for treatment success in settings where resistance is predicted by genotypic drug resistance results.
  • Studies focused on determining the biological basis for treatment failure in the setting where resistance is not predicted by standard genotypic testing and adherence is thought to be optimal. 
  • Studies of genotype-phenotype-clinical outcome correlations across various clades/subtypes (including in vitro studies using clinical samples), and different agents and combinations of agents.
  • Studies of the contribution of minor variants to drug susceptibility and virologic outcome, and the point at which minor variants become clinically relevant.
  • For the above types of studies, investigators are encouraged to test in vitro susceptibility of viruses with combinations of mutations found in clinical specimens, and to test not only in the presence of single drugs, but also with relevant combinations of antiretroviral drugs.

This initiative will not support:

  • Clinical trials, although the use of samples from prior clinical trials is encouraged.
  • Development of new cohorts, but use of samples from established cohorts is permitted.
  • Surveys of resistance, although existing samples may be used. 
  • Studies primarily focused on adherence. 
  • Studies of HIV resistance to neutralizing antibodies or other biologicals.

HIV and Hepatitis B Co-Infection: Advancing HBV Functional Cure Through Clinical Research

Program Announcement—proposed FY 2018 initiative

Contact: Christine Chiou

Objective: Hepatitis B virus (HBV) functional cure establishes effective sustained control of HBV infection without the need for lifelong HBV antiviral medicines. The scientific objectives of this funding opportunity announcement (FOA) are to fill scientific gaps needed to 1) inform HBV functional cure strategies by furthering our understanding of unique challenges impacting HBV and HIV co-infected hosts and 2) advance the discovery and development of novel HBV interventions that are safe and achieve a functional cure in HIV and HBV co-infected individuals. The FOA will also increase awareness of the need for HBV functional cure strategies useful in the context of immune deficiency challenges of HIV+ individuals.

The FOA addresses item 4, “HIV-associated comorbidities and co-infections” in NOT-OD-15-137, “NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding.” In accordance with the 2017-2020 HHS National Viral Hepatitis Action Plan, this FOA focuses research efforts to improve treatment among a high-priority, heavily impacted population–people living with HIV. Goal 2 of the 2017-2020 HHS National Viral Hepatitis Action Plan strives to reduce deaths and improve the health of people living with viral hepatitis and supports the advancement of research and development of new and more effective HBV therapies with a goal of identifying a cure for HBV.

Description: The FOA invites applications proposing clinical research to identify and better understand the unique challenges to achieving a functional cure in HIV+ co-infected hosts as well as advance the discovery and development of novel strategies to achieve HBV functional cure for HIV+ co-infected adult and pediatric populations. Although clinical trials and establishment of new cohorts will not be supported by this FOA, the leveraging of ongoing NIH or non-NIH supported clinical trials and cohorts to collect samples and data to address areas of research interests is encouraged.

Clinical research areas supported by this FOA include but are not limited to:

  • Studying the effect of HIV infection on the host’s ability to establish and sustain immune control of HBV infection to inform HIV/HBV functional cure clinical trials design.
  • Identifying factors critical to inducing an effective immune response to clear and maintain immunologic control of HBV in HIV+ individuals.
  • Elucidating the mechanisms responsible for and identifying factors predictive of HBV reactivation in HIV+ individuals.
  • Enhancing the understanding of how to prevent HBV relapse and immune reconstitution inflammatory syndrome in HIV+ individuals.
  • Identifying interventional targets and endpoints to inform effective HBV cure strategies in HIV+ individuals.
  • Evaluating the benefits and harm of initiating HBV interventions during different phases of chronic HBV infection (e.g., antivirals with dual HIV and HBV activity initiated during the immune-tolerant phase).
  • Studying the impact of chronic HIV and HBV co-infection on immune tolerance, immune activation, inflammation, and HBV viral persistence.

The FOA will not support:

  • Research that focuses on HBV in the absence of HIV.
  • NIH-defined clinical trials.
  • Establishment of new cohorts.
  • Studies of hepatitis other than HBV.
  • Animal or in vitro studies.

In Vitro and Animal Model Studies on HBV/HIV Co-Infection

Program Announcement—proposed FY 2018 initiative

Contact: Chris Lambros

Objective: The scientific objectives of this funding opportunity announcement (FOA) are to 1) stimulate and accelerate development of novel in vitro and small animal models to accelerate drug discovery/drug development in hepatitis B virus (HBV)/HIV co-infection and 2) stimulate and accelerate a better understanding of the immunopathogenic interactions between HBV and HIV leading to restoration of the host immune response to HBV using in vitro and small animal models of HBV/HIV co-infection.

The initiative addresses item 4, “HIV-associated comorbidities and co-infections” in NOT-OD-15-137, “NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding.”

Description: The FOA will invite applications proposing innovative, exploratory, and/or development of preclinical research on HBV/HIV co-infection. Research areas include but are not limited to:

  • Discovering/developing new in vitro test systems to enhance drug discovery/development in HBV/HIV co-infection.
  • Discovering/developing small animal models (e.g., mouse, rat) to enhance drug discovery/development for HBV/HIV co-infection that mimic the human co-infection.
  • Advancing our understanding of the pathogenic and immunologic interactions between HBV and HIV co-infection.
  • Evaluating the efficacy and safety of therapeutic interventions (to include immunotherapeutics, immunomodulators, vaccines, or combination of agents) in treating HBV/HIV co-infection.
  • Discovering/developing novel immune-based therapies (to include therapeutic vaccines) capable of eliciting an immune response and maintaining immunologic control of HBV infection in HBV/HIV co-infection.
  • Conducting basic molecular studies on HBV replication or HBV protein expression or their regulation in the presence of HIV infection.
  • Eliminating or suppressing HBV cccDNA.
  • Stimulating HBV-specific innate immune response in the presence of HIV.
  • Restoring HBV-specific adaptive immune response in the presence of HIV.

The FOA will not support:

  • Research that focuses on HBV in the absence of HIV infection.
  • Clinical trials.
  • Establishment of new cohorts.
  • Studies of hepatitis other than HBV.
  • Studies performed on human specimens (e.g., blood tissue) and collection of clinical information/data.

Methods To Increase Yields of HIV Envelope Protein Vaccine Manufacturing Through Cell Substrate Modifications or Through Novel Up- or Down-Stream Process Development Technologies

Note: NIAID topic for NIH SBIR contract solicitation.

Request for Proposals

Contact: Charles H. Jackson, Jr.

 

Content last reviewed on February 9, 2017