June 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

Genetic Engineering Technologies for HIV Cure Research

Request for Applications—proposed FY 2020 initiative

Contact: Sandra Bridges

Objective: The development of gene and cell-based approaches to achieve long-term remission or elimination of HIV that can eventually be evaluated in the clinic, rendered scalable, and deliverable.

Description:

Scope of the research includes:

  • Approaches to eliminate or inactivate integrated HIV provirus using genome- or epigenome-editing technologies.
  • Strategies to produce cells resistant to infection and/or cells with enhanced ability to eliminate HIV-infected cells (T cells, NK cells, blood stem or progenitor cells, novel allogeneic stem cell sources such as iPSCs, or other); ex vivo or in vivo gene modification approaches allowed. This would include developing gene therapies targeting new host targets for HIV.
  • Development of novel strategies, including underexploited novel viral or non-viral vectors plus physical delivery methods, for targeting therapies into HIV-infected cells or tissues where target cells reside (persistently or latently infected cells).
  • Combination studies that include one required cell or gene therapy modality; for example, a gene therapy with a drug or biologic, or HIV provirus excision plus a CAR-T cell therapy.
  • Novel approaches for improving transplantation and engraftment as well as minimizing rejection of modified cells as part of an HIV targeted transplantation strategy. For example, this could include developing non-toxic conditioning methods as well as other strategies for in vivo expansion, selection, persistence, and distribution of modified cells.
  • Proof-of-concept studies in animals. These studies could include efficacy studies in small animals on suppressive antiretroviral therapy, assessment of safety, drug-drug interactions, immunogenicity of modified host genes, and resistance development.
  • Pilot clinical studies (feasibility or safety studies): optional.

Nonresponsive:

  • Vaccines
  • CCR5 as a target unless part of a combination study that includes other possible viral targets
  • Investigational new drug (IND)-enabling studies, e.g., safety and toxicology (IND-enabling studies supported by other funding sources could be part of the overall development plan to move the therapy into the clinic)

Criterion for sunset of this program: when another program is developed that substantially fulfills the need of investigators working collaboratively in this scientific area.

Single-Cell Multi-Omics of HIV Persistence

Request for Applications—proposed FY 2020 initiative

Contact: Lillian Kuo

Objective: The scientific objective is to support hypothesis-driven basic science research to address outstanding questions in HIV latency and persistence by leveraging state-of-the-art single-cell multi-omics approaches. The goal is to interrogate HIV persistence with high molecular detail and fine grain resolution to better understand HIV persistence at the single-cell level. Single-cell analyses will illuminate molecular resolution and heterogeneity that is lost in population-level studies. These approaches will help to stimulate basic research characterizing pathways, factors, and biomarkers involved in HIV persistence, latency, latency reversal, killing of reservoir cells, viral rebound, and control of viremia.

Description: This initiative will support interdisciplinary basic science research using single-cell multi-omics approaches and bridging molecular virology and immunology, bioinformatics, and bioengineering. The goal is to gain mechanistic insight, not descriptive correlations. Traditional systems biology using cell populations or cell lines will be out-of-scope. Applications will have to use cells from HIV+ individuals and cannot rely solely on primary cell models of latency where cells are infected in vitro.

Emphasis will be on multi-omics or multiplex approaches integrating cutting-edge technologies including but not limited to CRISPR/Cas9 genetic screens, transcriptomics, epigenomics, and CyToF, combined with emerging single-cell technologies to characterize pathways, factors, and biosignatures involved in HIV persistence, latency, latency reversal, cell killing, viral rebound, and control of viremia. These studies will enable a better understanding of the distribution of intact, uninduced, replication-competent proviruses; clonal expansion and clonal dynamics; the contribution of “translation-competent” defective proviruses to persistence; and other high-priority basic science questions.

Simian Vaccine Evaluation Units

Request for Proposals—proposed FY 2020 initiative

Contact: Ashley Virts

Objective: The Simian Vaccine Evaluation Unit (SVEU) contracts facilitate the identification of promising AIDS vaccines by evaluating the immunogenicity and efficacy of candidate vaccines in nonhuman primates (NHPs). The ultimate objective is to provide information that will lead to the development of a human vaccine that can provide broadly reactive and long-lasting protective immunity against HIV infection.

Description: This initiative will support SVEU contracts to provide NHPs and appropriate facilities and staff to evaluate candidate HIV and prototype SIV vaccines. A variety of vaccine types, routes of delivery, routes of challenge, and challenge viruses will be evaluated to address relevant vaccine issues, identify vaccines that provide protection from infection or disease, understand the basis of that protection, and help elucidate the impact of immunization on the relevant stages of SIV/SHIV infection. The SVEUs will provide a responsive, efficient, and productive resource for conducting studies to inform vaccine design and the administration of vaccine evaluation trials in humans.

The government accepts AIDS vaccine candidates for SVEU evaluation from diverse investigators, including the NHP consortia, R01 and R21 grantees; HIV Vaccine Research and Design, Integrated Preclinical/Clinical AIDS Vaccine Development, Center for HIV/AIDS Vaccine Immunology investigators; and company-based researchers.

Clinical Research Products Management Center (CRPMC)

Request for Proposals—proposed FY 2020 initiative

Contact: Kishan Patel

Objective: This contract provides for the continued operations of a Clinical Research Products Management Center (CRPMC) needed to support NIAID’s clinical trials with the core focus of HIV/AIDS and its co-morbidities. This initiative will have options to provide limited support for clinical trials across NIAID. The CRPMC must adhere to current Good Manufacturing Practice (cGMP) and Good Clinical Practice. The contract requires full compliance with 21 CFR and ICH6 regulations as well as flexible and responsive communication systems between over 200 clinical sites worldwide, NIAID staff, and Network Leadership Groups. Cost-effective, timely, and regulatory compliant acquisition, receiving, processing, storage, and shipping are essential to meet investigational new drug sponsor’s obligations delegated to the contractor. The contract also provides expert services needed to evaluate and address clinical site pharmacy responsibilities and performance.

Description: This contract meets NIAID’s responsibility for the comprehensive management of study products essential to NIAID-sponsored clinical trials. In some cases, the contractor provides site pharmacy support.

These activities will include but are not limited to:

  • Provide and maintain physical facilities, equipment, and data systems for the full range of study product activities that are fully compliant with domestic and international regulatory requirements as well as U.S. federal information technology standards.
  • Provide a web-based, secure, accessible, and real-time clinical study product inventory management system.
  • Receive shipments of clinical study products (e.g., therapeutics, vaccines, biologics).
  • Store and maintain clinical study products under appropriate and secure conditions.
  • Provide expertise needed to facilitate importing and exporting clinical study products for international and domestic studies.
  • Distribute study products to authorized investigators both domestically and internationally.
  • Repackage clinical study products and/or package product kits for clinical trial protocols in accordance with cGMP and other applicable regulations.
  • Design product labels in compliance with FDA and international regulatory requirements and design.
  • Recall and process study product returns, which may include:
    • Returning study product to the manufacturer
    • Coordinating the destruction of unused study products as directed
    • Verifying unused quantities and witnessing product destruction at international sites
  • Provide clinical site pharmacy support, including review of site pharmacy monitoring reports and site pharmacy staff training for pharmacy and study product management.

Patient Safety Monitoring in International Laboratories (SMILE)

Request for Proposals—proposed FY 2020 initiative

Contact: Patrick Finn

Objective: This initiative is expected to provide a contractual resource that will continue to work with more than 170 mostly non-U.S. laboratories to support a comprehensive and uniform approach to evaluate initial and ongoing capability and readiness to carry out NIAID-funded and collaborative clinical trial protocols by 1) monitoring compliance with good clinical laboratory practice (GCLP) standards, 2) monitoring the quality and reliability of protocol-specified laboratory test results, and 3) providing labs with various means of assistance, guidance, and training to improve the quality of laboratory operations. This activity will continue to help achieve:

  • Safety of trial subjects
  • Safety of those performing the testing
  • Quality of trial laboratory data and accountability to regulatory organizations (FDA, European Medicines Agency) for investigational new drug/registrational studies
  • Increased recognition and appreciation of the fact that good laboratory practices lead to better general local laboratory operations and service
  • Cross-network/non-network harmonization in laboratory operations and oversight

Description: This initiative will:

  • Help laboratories achieve compliance with GCLP standards (e.g., DAIDS GCLP Guidelines, ISO 15189) for organization and personnel, verification of reagent and instrument performance specifications, quality management, equipment maintenance and facilities, and personnel safety. These ensure quality and integrity of safety and study data and accurate reconstruction of experiments. This aim will be accomplished through guidance for resolving laboratory audit findings/deficiencies, review of a lab's standard operating procedures (SOPs), and corrective action to avoid future deficiencies.
  • Determine the ability of laboratories to accurately and reliably perform all tests indicated in trial protocols (e.g., chemistry, hematology, pregnancy, HIV diagnosis, TB diagnosis). This will be accomplished by:
    • Purchasing the appropriate proficiency testing (PT) panels which include unknown (blinded) samples provided by an external source
    • Monitoring and grading PT results
    • Guiding labs in investigating root causes to prevent future failures
    • Helping labs correct deficiencies
  • Provide guidance and training to laboratories to achieve compliance with GCLP standards and test proficiency by email and phone communications, interactive web conferences, presentations at investigator meetings and regional training events, and visits of various duration to struggling laboratories.
  • Maintain a 508 and Federal Information Security Management Act-compliant web-based information repository that includes lab-specific documents such as records of resolution of each lab's audit findings and performance in proficiency testing panels, and a resource library that includes guidance document and SOPs for various laboratory procedures. Examples of resource documents include a checklist and guidance for moving a lab to a new location, how to validate instruments, and how to ensure the safety of laboratory technicians. The contractor will provide each participating laboratory with controlled access to its own documents and provide NIAID and Network lab managers with controlled access to all documents.
  • Generate lab-specific reports for each lab indicating the degree of performance for each round of proficiency testing; summary reports indicating, for DAIDS and the Networks, the proficiency status of all laboratories; and trimester progress reports.

Data Management and Data Warehousing

Request for Proposals—proposed FY 2019 initiative

Contact: Kate Stotish

Objective: This contract will provide and support Clinical Data Management System (CDMS) and Data Warehousing and Reporting Tools (DWRT) for clinical studies implemented by the Vaccine Research Center’s (VRC) Clinical Trials Program (CTP) and collaborators.

Description: This initiative will support a CDMS and DWRT for clinical research to provide comprehensive and consistent data management support for the VRC’s CTP. The CTP implements natural history, therapeutic, and preventative clinical trials to test candidate products such as vaccines and immunomodulators for a range of infectious diseases. These services may be provided for trials activated at single or multiple sites that are domestic and/or international.

Specifically, the contract will provide a comprehensive array of data management support services, including protocol-specific web-based data collection plans/programming, management, and quality control; statistical consultation and reporting, design, and analysis; assistance in study materials development with related web-based reports and training; creating Data Collection Forms, electronic specimen tracking; adverse events dictionary and reconciliation, providing Regulatory Tracking System, and data reports to support safety/regulatory/security requirements and report on study progress. The contract will also create, manage, and maintain a secure, compliant repository for current and historical clinical trials outcomes data and analyses, while allowing instant accessibility of integrated and standardized data via advanced analytics and visualization reporting tools with web-based access.

Approaches for Understanding Disease Mechanisms and Improving Outcomes in TB Meningitis

For the published program announcement with special receipt, referral, and/or review considerations, see the June 7, 2018 Guide announcement, Approaches for Understanding Disease Mechanisms and Improving Outcomes in TB Meningitis (TBM) (R01, Clinical Trial Not Allowed).

Characterization of Mycobacterial Induced Immunity in HIV‐Infected and Uninfected Individuals

Program Announcement With Special Receipt, Referral, and/or Review Considerations—proposed FY 2019 initiative

Contact: Cesar Boggiano

Objective: The goal of this announcement is to encourage innovative studies to identify and understand the immunological responses that mediate protection from Mycobacterium tuberculosis (Mtb) infection or progression to active disease. Such responses may be operative in mycobacterial infection or following vaccination with Bacillus Calmette-Guérin (BCG) or investigational vaccines, and may have distinct relevance to HIV-infected or uninfected individuals. Studies with human cells and tissues are encouraged and can include samples from both HIV-infected or uninfected individuals. Research using well-justified animal models is also acceptable. Research approaches of interest, which go beyond descriptive information currently known about Mtb infection and responses to vaccines, include but are not limited to:

  • Development of novel functional assays to assess the host immune response against mycobacterial infections or candidate vaccines to increase information output and/or significantly minimize the amount of samples needed for a given evaluation
  • Elucidation of mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms, throughout the course of mycobacterial infection/disease or vaccination
  • Analysis of innate immune pathways and mechanisms in response to mycobacterial infection or tuberculosis (TB) vaccination, including the effect on down-stream activation of adaptive immune responses
  • Identification and analysis of immune response elicited during TB infection that may benefit mycobacterial persistence
  • Analysis of efficacy trials samples evaluating TB vaccine candidates to identify immune correlates of protection or disease progression
  • Effect of prior exposure to mycobacteria (Mtb or nontuberculous mycobacterials) or BCG vaccination on subsequent immune responses to Mtb infection, TB reactivation, disease reoccurrence, or TB vaccination

Description: The field of TB vaccine development has been hampered by a lack of opportunities to study novel and high-risk questions addressing Mtb immunity and immune evasion in humans. This is because most immunological paradigms of host/pathogen interactions have been established in animals with limited validation in humans, providing limited insight into clinical relevant aspects of mycobacterial immunity and immune evasion such as spatial and temporal immune responses and their regulation.

This initiative is designed to facilitate hypothesis-generating science in innovative, potentially dogma changing areas of TB vaccine design.

CNS‐Targeted Drug Delivery Strategies for HIV

Program Announcement With Special Receipt, Referral, and/or Review Considerations—proposed FY 2019 initiative

Contact: Marina Protopopova

Objective: The objectives of this initiative are consistent with the Division’s priorities:

Next generation of HIV therapies with better safety and ease of use

  • Developing and testing HIV treatments that are less toxic, longer acting, have fewer side effects and complications, and easier to take and adhere to than current regimens.

Research toward a cure

  • Developing novel approaches and strategies to identify and eliminate viral reservoirs that could lead to a cure or lifelong remission of HIV infection, including studies of viral persistence, latency, reactivation, and eradication.

Description: The purpose of this funding opportunity announcement (FOA) is to encourage investigators to explore novel central nervous system (CNS)-targeted drug delivery platforms and focus on product development activities to identify and eliminate viral reservoirs that potentially lead toward a cure or lifelong remission of HIV infection. This FOA will support all stages of nonclinical product development activities to yield new preparations of anti-retroviral drugs (ARVs) with suitable balance between efficacy and safety.

Applications are sought in two specific areas:

1. Development of formulations for CNS-targeting of existing ARVs
2. Development of formulations with the ability to carry large molecules (e.g., proteins, broadly neutralizing antibodies, bi-specific antibodies) to the CNS for HIV inactivation or for purging of the CNS reservoir

Efforts to develop new CNS-targeted drug delivery platforms must be guided by critical assessments of neurotoxicity and their potential impact on product safety. Investigators are encouraged to use a multidisciplinary approach and include both in vitro and in vivo studies to assess the activity, pharmacological profiles, and potential toxicity.

The following activities will not be considered for support:

  • Clinical trials
  • Discovery of new drugs or biologics for HIV

Engaging Men in HIV Testing, Prevention, and Care

Program Announcement—proposed FY 2019 initiative

Contact: David Burns

Objective: The proposed program announcement will invite applications to develop and test strategies to increase the engagement of men in HIV prevention and care, in both domestic and international settings where there are lower rates of engagement and retention of men in HIV prevention and care.

Description: This proposed initiative will be focused on developing effective strategies to recruit, engage, and retain men in HIV prevention and care and assessing the impact of these treatment and prevention strategies along the HIV prevention and care continua. It also calls for pilot research on the feasibility, acceptability, and preliminary outcomes for the strategies developed for men. Additionally, a focus will be on modeling the potential impact of successful strategies if implemented across different communities and regions. Companion funding opportunity announcements will be issued for the R01 and R21 grant mechanisms. The R01 mechanism is intended to support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing the investigator’s specific interest and competencies. The R21 grant mechanism is intended to encourage exploratory/developmental research by providing support for the early and conceptual stages of project development.

Next Generation Multipurpose (NGM) Prevention Technologies

Program Announcement With Special Receipt, Referral, and/or Review Considerations—proposed FY 2020 initiative

Contact: Jim Turpin

Objective: The objectives of this initiative are consistent with the overarching NIH AIDS Priorities outlined in NOT-OD-15-137, NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding.

Reducing Incidence of HIV/AIDS including: developing and testing promising vaccines; developing and testing microbicide and pre-exposure prophylaxis candidates and methods of delivery, especially those that mitigate adherence issues; and developing, testing, and implementing strategies to improve HIV testing and entry into prevention services.

Description: This initiative will support the developing multipurpose prevention technologies (MPT) for preventing pregnancy and sexually transmitted infections (STI). For the purposes of DAIDS, the focus will be on licensed contraceptives combined with anti-HIV drugs (licensed or unlicensed). Applicants may propose any combination of a prevention and contraception product that uses a sustained release platform to provide the minimal windows of efficacy/protection identified below. The overarching objective will be to establish a pipeline of MPT candidates.

All proposed MPT approaches must address a minimal window of protection of 30 days or 1 menstrual cycle from either a single dose regimen (injection) or continuous dosing regimen (e.g., implant, transdermal patch). Development of longer durations of protection and durations congruent when a licensed contraceptive is incorporated into the MPT will be encouraged. Co-packaging as an MPT strategy of an existing licensed hormonal contraceptive and a licensed antiviral strategy will be discouraged.

Clinical trials are optional. When clinical trials are proposed, they are expected to concentrate on identifying Preferred User Characteristics (PUC) to increase potential user’s adherence. PUCs are defined as the look and feel properties of the sustained drug delivery system that will influence potential user’s decisions for initial, continued, and habitual use. Clinical trials posed solely for first-in-human testing and/or to determine the safety/efficacy of proposed MPTs will be actively discouraged.

Sustained Release of Antivirals for Treatment or Prevention of HIV (SRATP)

Program Announcement With Special Receipt, Referral, and/or Review Considerations—proposed FY 2020 initiative

Contact: Jim Turpin

Objective: The objectives of this initiative are consistent with the Division’s priorities:

  • Halt the spread of HIV infection by defining highly effective prevention strategies, including a preventive vaccine
  • Cure HIV infection
  • Improve outcomes of treated HIV disease

Description: This initiative will support developing sustained release strategies for HIV prevention and treatment. Applicants may propose any combination of prevention and treatment products and sustained release platforms that will provide minimal windows of efficacy/protection identified below. The overarching objective will be to establish a pipeline of sustained release prevention and treatment candidates.

To meet the sustained release needs of the treatment and prevention fields the following definition and types of sustained release will be solicited:

1. Treatment sustained release: Oral therapy sustained release strategies must have a window of effectiveness of at least seven days from a single dose. Other sustained release approaches for therapy must have a minimal window of protection of 30 days from either a single dose regimen (injection) or continuous dosing regimen (implant, transdermal patch).
2. Prevention sustained release: All sustained release strategies designed to prevent HIV infection must have a minimum window of protection of 30 days from either a single dose regimen (injection) or continuous dosing regimen (implant, transdermal patch).

For all forms of sustained release development, applicants are encouraged to develop sustained release strategies that provide longer windows of therapy or protection than the minimal windows identified above.

Content last reviewed on June 18, 2018