NIAID will support large, electronically generated cohorts of HIV-negative men who have sex with men (MSM), transgender women (TGW), people who inject drugs (PWID) and other groups at increased risk of HIV acquisition in Latin America through the notice of funding opportunity (NOFO) Limited Interaction Targeted Epidemiology: Epidemiology of Transmission and Treatment of HIV Among People Who Are at Increased Risk for HIV Infection in Latin America (LITE-LA) (UG3/UH3, Clinical Trial Optional).

Interested researchers can apply for funding to study the epidemiology of viral HIV suppression and determine study approaches or evidence-based digital treatment interventions to reduce HIV transmission in Mexico and South and Central America.

Research Objective and Scope 

The primary goal of this NOFO is to generate information to develop health interventions to reduce HIV transmission in Mexico and South and Central America. Continued follow-up of people living with HIV (PLWH) should be conducted to study the epidemiology of viral suppression. 

This NOFO allows digital, clinical, non-investigational new drug application trials to determine optimal study approaches or pilot evidence-based digital HIV prevention and treatment interventions to reduce HIV transmission. There is increasing evidence that use of digital interventions, delivered online or through smartphones, can advance primary HIV prevention outcomes such as reduced sexual risk behavior, decreased sexually transmitted infections (STIs), and improved use of oral or long-acting pre-exposure prophylaxis (PrEP). 

To inform the treatment of HIV in Latin American countries, include comparison of participants with HIV who become engaged in care and reach non-detectable HIV levels to those whose virus remains detectable.

Studies of interest include:

• Identification of micro-epidemics in high HIV transmission areas (hot spots) and of key sub-populations where HIV prevention and treatment efforts in Latin America are most needed.
• Characterization of subgroups of PWID, female sex workers, transgender persons, and MSM who could be prioritized for HIV prevention and improved treatment strategies.
• Description of risk behaviors and risk determinants in these key populations that can inform onward interventions to reduce HIV incidence.
• Studies using the assembled cohorts to investigate patterns of HIV testing and mechanisms to optimize testing frequency and rapid linkage to treatment.
• Monitoring HIV PrEP or undetectable equals untransmitable (U=U) awareness, uptake, and adherence and identifying associated determinants.
• Mental health as a determinant of HIV exposure risk and engagement in prevention and treatment of HIV.
• Multi-level analyses of individual and social-contextual determinants of HIV risk behavior, seroconversion, or reaching viral suppression of HIV.
• Development and testing of scalable, digitally delivered primary HIV prevention interventions that promote HIV risk reduction and may include support for PrEP use or viral suppression of HIV-positive sex partners among high-risk groups through digital clinical trials.

NIAID will consider applications including the following types of research to be nonresponsive and not review them:

• Studies limited to studying PLWH.
• Studies of subjects residing outside Mexico and South or Central America.
• Studies not including a co-investigator from each country in Latin America providing participants.
• Studies not proposing the use of technology-focused approaches to establish and follow cohorts of HIV-negatives for epidemiologic research.
• Studies not focused on at least one of the high-incidence groups prioritized by the NOFO: MSM, female sex workers, transgender persons, or PWID.
• Studies not including an analysis that demonstrates that the expected statistical power of their planned investigations will be adequate.
• Studies planning to enroll fewer than 5,000 individuals without HIV during the UG3 phase.
• Studies proposing a clinical trial that requires an investigational new drug application.
• Studies lacking clearly described timelines for the UG3 and UH3 phases and studies lacking clearly defined and quantifiable Go/No-Go transition milestones.

UG3/UH3 Phased Innovation Awards 

Applications must be structured around two phases. The UG3 phase provides 2 years of support for enrollment of sufficient numbers of participants from high-incidence populations. The UH3 phase provides an additional 3 years of support to conduct research to advance our knowledge of when, where, why, and how HIV transmissions currently occur in Latin America. 

At the end of the UG3 phase, NIH staff will assess Go/No-Go transition milestones accomplishment, preparedness of the cohort to implement the proposed epidemiology and the optional intervention studies, programmatic priorities, and available funds to determine a transition to the UH3 award. UG3 phase funding does not guarantee support of the UH3 phase award for research implementation. 

Applicants proposing clinical trials must include the available information and describe the plan, including the timeline for developing final versions in time to implement the clinical trial within the first 12 months. For a list of the five required attachments, read Section IV. Application and Submission Information of the NOFO.

Budget Information

NIAID plans to fund one or two awards. Application budgets are not limited but need to reflect the actual needs of the proposed project. The project period may be up to 5 years; up to 2 years for the UG3 phase and up to 3 years for the UH3 phase. 

Application Deadline

Applications are due on July 30, 2024, by 5 p.m. local time of the applicant organization. 

Contact Information 

Send inquiries to NIAID’s scientific/research contact, Dr. Gerald Sharp, at GSharp@niaid.nih.gov or 240-627-3217. Send any peer review related inquiries to NIAID’s peer review contact, Dr. Robert Unfer, at Robert.unfer@nih.gov or 301-641-1981.

NIAID aims to advance true point-of-care (POC) diagnostics for tuberculosis (TB)—including rapid drug-susceptibility testing (DST) in decentralized settings, targeted pediatric diagnostics that include non-sputum-based diagnosis, and technologies to improve the diagnosis of TB among people living with HIV (PLWH), including disseminated and paucibacillary TB.

Through Feasibility of Novel Diagnostics for TB in Endemic Countries (FEND for TB) (R01, Clinical Trial Not Allowed), we will support proof-of-principle studies to evaluate novel, early-stage TB diagnostic tests, assays, and strategies, validate biomarkers, and provide feedback to diagnostic developers and policy makers on the performance of the technology as well as potential strategies for use of novel technologies in endemic settings.

Partnership with Existing Sites

To accomplish the goals of this initiative, applicants should propose a partnership of investigators and existing clinical study sites in TB endemic countries, coordinated and led by a leadership team, to evaluate early-stage TB diagnostics. The clinical sites must provide access to adult and pediatric study populations with drug-susceptible and drug-resistant TB, and should include populations with co-morbidities including PLWH.

The leadership team will organize, coordinate, and provide oversight for study implementation to evaluate TB diagnostics and will implement a process to identify and prioritize TB diagnostics and biomarkers to be evaluated under the grant, including a process for technology holders to submit requests for diagnostic evaluations.

Your application must include at least one foreign clinical study site located in a TB-endemic country. Study sites should have the facilities and personnel necessary to carry out study-specific laboratory testing in accordance with Good Clinical Laboratory Practice guidelines, store patient samples under appropriate conditions, and diagnose TB according to the current standard of care.

Priority Diagnostics

In your application, you must identify one or more early-stage diagnostics ready for initial testing in the first year of performance and include detailed plans to evaluate additional diagnostics in subsequent years.

NIAID has highlighted diagnostics of interest, including:

• POC or near-to-care tests.
• Diagnostics for use in underserved populations, including children and persons with disseminated or paucibacillary TB disease and PLWH.
• Product candidates that identify TB using specimens other than sputum (e.g., blood, serum, urine, stool, breath, swabs) allowing identification of paucibacillary or extrapulmonary TB in adult and pediatric patients.
• Diagnostics that may overcome limitations such as cost and infrastructure associated with current molecular diagnostic approaches.
• Diagnostics that provide expanded rapid DST, including at the POC.
• Studies to evaluate the performance of diagnostics or host biomarkers in PLWH and people who are not living with HIV.
• Diagnostics that distinguish between vaccinated individuals and those who are infected with TB.

Diagnostic technologies for evaluation may detect TB across the disease spectrum, including identification of asymptomatic or subclinical disease, disseminated extra-pulmonary disease, and paucibacillary disease.

Applications may propose to conduct limited laboratory assessments of a diagnostic prototype to ensure performance and feasibility prior to conducting a clinical evaluation.

However, applications may not include any of the following activities; if an application does, we will consider it nonresponsive and not review it:

• Establishing new clinical infrastructure.
• Establishing a public biorepository (though samples may be stored and used in studies by the study team).
• Developing a new diagnostic prototype.
• Conducting a clinical trial.

In your application, describe your plans to incorporate the following elements into your FEND research program:

• Administration and Leadership Team—to organize, coordinate, and oversee the implementation of studies to evaluate TB diagnostics.
• Clinical Study Sites—to evaluate new TB diagnostics by leveraging established relationships with local clinicians.
• Clinical Support Team—to coordinate procedures related to recruitment, enrollment, and data and biological sample collection at individual enrollment sites.
• Data Stewardship and Analysis Team—to develop and implement procedures for the collection, oversight, and inventory of data and biological samples.
• External Advisory Committee (EAC)—to review progress and share recommendations with NIAID as part of annual programmatic meetings.

FEND investigators and key personnel, NIAID staff, and EAC membership will attend the annual programmatic meetings to facilitate collaborations, provide progress reporting, seek new research directions and ideas, and update NIAID on issues of need. Further, FEND researchers will participate in quarterly virtual programmatic meetings to discuss ongoing and future activities.

Application Requirements

Your budget request should not exceed $3.5 million in annual direct costs. Your proposed project period must be 5 years.

Foreign organizations are eligible to apply.

The notice of funding opportunity has a single due date: June 28, 2024, at 5 p.m. local time of the applicant organization.

The Centers for Research in Emerging Infectious Diseases (CREID) Network works to expand knowledge of re-emerging and emerging infectious diseases (re/EIDs) around the globe where outbreaks are most likely to occur while developing expertise, capacity, and readiness to address outbreak-related research. 

Each CREID Research Center (RC) hosts multi- and interdisciplinary teams of domestic and international investigators to conduct innovative, hypothesis-driven One Health-based research, undertake outbreak-related research when necessary in its geographical area, and work across the CREID Network in a coordinated, collaborative, and cooperative fashion. Additionally, a Coordinating Center (CC) serves to lead, advance, and facilitate critical scientific, data, and resource management activities during both outbreak and non-outbreak periods among the CREID Network RCs.

There are two notices of funding opportunities (NOFOs) through which you may apply, to propose either a Research Center or the Coordinating Center, respectively:

• Centers for Research in Emerging Infectious Diseases (CREID) Network (U01, Clinical Trial Not Allowed)
• Centers for Research in Emerging Infectious Diseases (CREID) Network Coordination Center (U01, Clinical Trial Not Allowed)

NIAID’s aim is to support six to eight RCs and a single CC.

CREID Scientific Priorities

CREID Network RCs must take a comprehensive research approach. Each RC must incorporate both animal and human subjects elements, and may include other elements such as vectors or climate and environment. The human based elements of the research may leverage human subjects cohorts, either short-term (e.g., acute febrile illness) or long-term/longitudinal cohorts, as well as archived clinical specimens. 

Examples of possible research topics include:

• Pathogen discovery and characterization.
• Pathogen surveillance in animals, vectors, and humans as it relates to assessment of prevalence, molecular epidemiology, or other priorities within CREID’s purview.
• Evaluating factors related to pathogen transmission, maintenance, emergence, adaptation, and evolution as related to human infections.
• Defining the contemporary spectrum of clinical disease presentation and progression, pathophysiology, and clinical outcomes of infection in humans (including sequelae) or determinants of disease severity.
• Human immunologic responses to the infection.
• Modeling emergence risk.
• Development of reagents, diagnostic/detection tools, and critical animal models.
• Research that is foundational or translatable to further development of medical countermeasures to important human health re/EIDs.

You may study any emerging pathogen (viral, bacterial, or eukaryotic), but your primary focus should be on viral infectious pathogens most likely to emerge or re-emerge in humans. Further, you are required to work on at least one viral pathogen from the NIAID Emerging Infectious Diseases/Pathogens list, which includes members of viral families Arenaviridae, Coronaviridae, Flaviviridae, Filoviridae, Hantaviridae, Nairoviridae, Paramyxoviridae, Peribunyaviridae, Phenuiviridae, Picornaviridae, and Togaviridae that are not already studied by other NIAID-funded networks (e.g., HIV, influenza, malaria) and for which countermeasures are not developed or are suboptimal.

We also encourage you to propose working in at least two geographic regions with at least one located within a tropical or subtropical region, with a goal of establishing research sites in targeted areas of the globe such as South and Central America, Sub-Saharan Africa, and Southeast Asia. 

Conversely, you must not apply to conduct:

• Genome-wide association studies
• Projects where behavioral research is the primary focus
• Projects that include product development research or advancement of vaccines or antivirals
• Clinical trials

Refer to the first NOFO linked above for complete details of CREID’s scientific priorities, including a full explanation of how you can best pinpoint research topics for your proposed center that will complement existing NIAID international research efforts.

Strict on Structure

In your application, you should provide for an Administration and Leadership Team, a Data Stewardship and Analysis Team, and a Clinical Research Support Team (excepting the CC). Each of these elements are detailed in the NOFOs.

Further, you must address plans for coordination, collaboration, and cooperation within the CREID Network; strategies to strengthen the CREID Network’s research capacity; and a plan to develop and manage an Opportunity Fund, which is meant to strengthen the impact of shared or complementary topic research, preparedness and outbreak-related research and activities, and other activities or efforts that further CREID's collaborative objectives and goals.

Additionally, the CC will develop and manage a capacity strengthening and pilot research program with the goals of developing research infrastructure, scientific expertise, and the next generation of re/EID scientists and leaders globally.

Application Requirements

Review the NOFOs linked above for a complete listing of application requirements, e.g., your application budget must reflect the actual needs of the proposed project. Note that, for both NOFOs, you must propose a 5-year project period. 

New and renewal applications are allowed. 

Foreign organizations are eligible to apply. 

For both NOFOs, there is a single due date on June 21, 2024, at 5 p.m. local time of the applicant organization.

Direct questions to Dr. Sara Woodson, the NOFOs’ scientific/research contact, at woodsonse@niaid.nih.gov or 301-761-6478.

For matters related to peer review of RC applications, contact Dr. Annie Walker-Abbey at aabbey@niaid.nih.gov or 240-627-3390; for matters related to peer review of CC applications, contact Dr. Mairi Noverr at mairi.noverr@nih.gov or 240-987-1668.