Key Dates

Related Announcements

• May 10, 2021 - NIMH Exploratory/Developmental Research Grant (R21 Clinical Trial Not Allowed).  See NOFO PA-21-235
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed).  See NOFO PA-20-195
• May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).  See NOFO PA-20-185

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Mental Health (NIMH)

Purpose

This Notice of Special Interest (NOSI) is to highlight NIAID’s interest in HIV cure-related research in diverse cohorts of people living with HIV to determine similarities and differences in the establishment and dynamics of persistent non-subtype B HIV reservoirs, as well as in post-treatment control of viremia.

Background and Goals

Most cure-related research on HIV has been limited to subtype B virus, which constitutes the majority of infections in North America, South America, Australia, and Western Europe, with the highest prevalence in cisgender men who have sex with men (MSM). In the United States, although subtype B is predominant, the prevalence of non-subtype B HIV is increasing. Among the 38 million people living with HIV globally, subtype B represents just 12% of the total burden of HIV. Subtype C virus constitutes the highest proportion of infections (47%), with the highest prevalence in cisgender women living in Sub-Saharan Africa. Almost 70% of all people living with HIV worldwide live in Sub-Saharan Africa and over 50% are cisgender women.

Some evidence suggests that the frequency of viremic control in the absence of antiretroviral treatment (ART) may be higher in females and in some populations in which non-subtype B virus is predominant. Additionally, one study of replication-competent persistent reservoirs in subtype C infection in Uganda demonstrated a smaller overall reservoir size as compared to individuals with subtype B infection in the U.S. These few studies indicate more research is needed to understand how HIV reservoir dynamics and immune control vary in diverse populations.

Research Objectives

National Institute of Allergy and Infectious Diseases (NIAID) encourages applications in basic, preclinical, or clinical research studies using existing human samples to analyze and compare HIV human reservoir establishment, dynamics, persistence, and post-treatment control in diverse cohorts of people living with HIV. The proposed studies should include particular emphasis on the impact of viral subtype, sex, age, coinfections and comorbidities, and geography. Studies including samples from people living with HIV in low- and middle-income countries (LMICs) are encouraged.

Studies designed to develop and utilize relevant, non-subtype B HIV model systems and assays will also be supported. Under this NOSI, clinical trials are not allowed, but the use of existing samples from clinical trials are encouraged, particularly longitudinal samples from participants on ART that underwent a treatment interruption.

Examples of research activities of interest include but are not limited to:

• Comparative studies to detect, quantify, and define HIV reservoirs in different cell types and tissues in diverse cohorts of people living with HIV on ART
• Comparative analysis of longitudinal HIV reservoir dynamics, including decay rates, distributions of persistent, actively expressing and latent reservoirs, viral integration sites within the genome, and mechanisms of clonal expansion in diverse cohorts of people living with HIV on ART
• Characterizing post-treatment control in diverse cohorts of people living with non-subtype B HIV
• Analyzing the effects of common comorbidities and coinfections in diverse populations of people living with HIV on reservoir establishment, dynamics, and persistence and/or on post-treatment control of viral rebound
• Determining the reactivation potential of latent, non-subtype B HIV in different cell types utilizing existing and/or novel latency reversing agents (LRAs)
• Research to define viral determinants affecting immune-mediated clearance of non-subtype B viral reservoirs

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) encourages applications that primarily focuses on HIV-1 reservoirs in anatomical sites relevant to its mission, particularly the gastrointestinal mucosa, liver, kidney, male genital tract, and adipose tissue depots including those at ectopic sites. In addition, prevalent NIDDK-related comorbidities and coinfections can impact the HIV-1 reservoir through inflammatory pathways, metabolic perturbations, or other pathophysiological processes. Therefore, NIDDK is also interested in research on how comorbidities and coinfections within its mission impact HIV-1 reservoir dynamics and immune control.  NIDDK-relevant comorbidities and coinfections include enteropathy and the loss of gastrointestinal homeostasis; noncommunicable liver diseases and viral hepatitis coinfections; kidney, urologic, and hematologic diseases; and obesity, diabetes, and associated complications. In addition to affecting the HIV-1 reservoir in affected tissues, NIDDK-relevant pathogenesis might impact reservoirs in other tissues and organ systems.  For example, HIV-associated enteropathy or obesity might have an impact beyond the gastrointestinal mucosa or adipose tissue reservoirs.  Diabetes and other metabolic perturbations might impact reservoirs in multiple tissues. Therefore, while projects are expected to interrogate NIDDK-relevant reservoirs, additional tissue reservoirs may be included along with them.

National Institute of Mental Health (NIMH) encourages HIV-1 cure related research in diverse cohorts of people living with HIV to determine similarities and differences in the establishment and dynamics of persistent non-subtype B reservoirs as well as post treatment control of viremia in the central nervous system (microglia, macrophages, astrocytes).

Applications proposing any of the following will NOT be supported under this NOSI:

• Focus solely on subtype B HIV without comparing diverse cohorts of individuals living with non-subtype B HIV
• Investigate HIV pathogenesis alone without a persistent reservoir or post-treatment control component
• Studies that involve animal models without a comparison to samples derived from humans
• Do not include analyses to distinguish replication-competent HIV from defective proviruses in reservoir studies
• Do not include analyses of human-derived samples
   

Application and Submission Information

This Notice applies to due dates on or after September 7, 2023, and subsequent receipt dates through May 7, 2026.

Applicants must select the IC and associated NOFO to use for submission of an application in response to the NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that NOFO. Non-responsive applications will be withdrawn from consideration for this initiative. In addition, applicants using NIH Parent announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those NOFOs are acceptable and based on usual application-IC assignment practices.

The following notice of funding opportunities (NOFOs) or their reissued equivalents must be used for submissions for this initiative. Although NIDDK is not listed as a Participating Organization in all the NOFOs listed below, applications for this initiative will be accepted where indicated for NIDDK.

All instructions in the SF424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-AI-23-046” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Leia Novak, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7825
Email: Leia.Novak@nih.gov

Jeymohan Joseph, PhD
National Institute of Mental Health (NIMH)
Telephone: 240-627-3869
Email: jjeymoha@mail.nih.gov

Peter J. Perrin, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-3759
Email: peter.perrin@nih.gov