amfAR, The Foundation for AIDS Research

Target Grants

Request for Proposals

Overview

Purpose
The goal of this RFP is to generate vital basic and preclinical data relevant to future HIV curative interventions.

Available funding
Grants provide funding of up to $200,000 (including indirect costs at a maximum rate of 20%) over a two-year performance period beginning on July 1, 2020.

Expected outcome
Basic and preclinical biomedical research findings that provide the foundation for new approaches to an HIV cure.

Eligibility
HIV researchers holding a doctoral degree and affiliated with nonprofit research institutes are eligible to apply.

Details

Background and Purpose

amfAR’s research initiatives are aimed at finding a cure for HIV that will be useful to the 38M people living with HIV. The urgency of our goal demands that we direct our funding to studies that uncover vital knowledge directly applicable to curing HIV.

Persistent reservoirs of virus not cleared by antiretroviral therapy (ART) represent the main barrier to a cure. amfAR intends to fund research that explores all curative approaches, including reservoir removal, elimination of mechanisms that sustain the reservoir, editing the provirus sufficiently to render it benign, or suppressing the intact provirus, thus preventing pathogenicity.

Outcomes of research funded through this RFP are expected to inform the design of new approaches to curing HIV.

Although applicants may submit research plans exploring any area of basic or preclinical research relevant to providing the foundation for new approaches to an HIV cure, the following represent particular areas of interest:

 

          1. Generate preclinical models that predict clinical trial outcome

A range of pharmacological, immune therapy and cell/gene therapy interventions have been tested in clinical trials for their ability to reduce, control or clear the persistent HIV reservoir. By and large, these clinical trials have resulted in, at best, modest detectable changes in the reservoir, despite preclinical data that provided reason to expect qualitatively or quantitatively better outcomes. 

As clinical trials become more common and large numbers of participants are enrolled, the lack of reliable “gatekeeper” or “go/no-go” assays will make decisions regarding the prioritization of resources for clinical trials increasingly challenging.

This funding opportunity calls for the development of preclinical models that can reliably predict clinical trial outcomes. By using participant-level data from completed clinical trials, applicants will propose to “retrofit” models that would have predicted the per-participant outcomes in at least two clinical trials of interventions that may be similar, but not identical (e.g., trials of two different therapeutic vaccines, but not two trials of the same therapeutic vaccine). The models may incorporate in silico, in vitro, ex vivo, or animal model components, or a combination of these, with the goal of optimizing predictive power while minimizing model/assay complexity.

Applicants will ideally propose to use clinical trial datasets in which participants experienced a range of endpoint outcomes. Models that can predict differential outcomes according to demographic variables such as sex, age, race/ethnicity, or viral clade/subtype may prove especially interesting.

This funding opportunity does not support the generation of new clinical data, e.g., via observational or interventional studies in humans.

 

          2. Use provirus to elicit destruction of cellular reservoir

In the absence of a surface marker that differentiates reservoir cells from other cells, we may be able to use the provirus, or even viral transcripts, as biomarkers to target interventions that specifically reduce, control or eliminate the reservoir.

Direct excision of proviral DNA represents one way to use the provirus as a marker of reservoir cells, and several such lines of investigation are already underway. However, this funding opportunity is aimed particularly at alternative methods of using the presence of provirus as a marker that can be exploited for specific killing of reservoir cells. These may include the use of technologies that rely on the presence of specific DNA or RNA, such as dCas, DNA-binding transcriptional regulators, RNAi, triplex DNA, global transcription machinery engineering (gTME), engineered synthetic transcription factors, or other such technologies. Alternatively, viral transcripts may be used as on- or off-switches for therapeutics designed to inactivate or destroy the provirus or reservoir cell. Applicants are also encouraged to submit research plans using HIV DNA- or RNA-dependent technologies not listed here.

 

          3. Characterize and manipulate reservoir cell environment

The establishment and persistence of a reservoir cell may be affected by immune as well as non-immune factors (cells and extracellular matrix) in its immediate environment.

Much is known about immune factors that shape the reservoir. Less studied are the potential effects of non-viral and non-immune mediators. Cells or soluble factors in the immediate vicinity of reservoir cells may affect cell metabolism or other cell-intrinsic function, trafficking, proliferation, expansion, persistence, or crucial cell-cell interactions. Examples of such factors may include the availability of pro-survival factors (e.g. nutrients, oxygen), chemical or cellular matrix surrounding the reservoir, or the presence/activity of parenchymal cells.

Applicants are encouraged to design research plans that characterize the non-immune environment of reservoir cells with the ultimate goal of to reducing, controlling or eliminating the reservoir.

Proposal Requirements 

amfAR will not consider iterations of previously tested ideas that resulted in only modest advances or studies that would result in incremental knowledge. Collaborations must be meaningful and capitalize on the verifiable expertise of all parties. This RFP does not fund prevention studies or non-biomedical research-based activities. 

If you are unsure whether your proposal fits amfAR’s grant topics, please e-mail your inquiry to grants@amfar.org.

Expected outcomes

Basic or preclinical biomedical research findings that provide the foundation for new approaches to an HIV cure.

Eligibility 

HIV researchers holding a doctoral degree and affiliated with a nonprofit research organization are eligible to apply. If the proposal is a collaboration including subcomponent projects, the Principal Investigator will be expected to lead one of the components and coordinate the implementation and analyses of the projects as a whole, and be responsible for overall financial management and submission of required reports.

Applications are accepted from nonprofit research institutions worldwide.  Applications are not accepted from individuals or for-profit entities.  Proposals may include subcontracts or sub-awards to for-profit organizations.

Submission Process and Application Review

Selection of funded applications is a four-step process, as follows:

1. Letters of Intent (LOIs) are reviewed by amfAR staff to ensure that: a) eligibility requirements are met; b) the research proposed is in line with amfAR objectives; and c) it is responsive to the RFP. LOIs that meet these criteria proceed to peer review.

2. LOIs are reviewed by leading HIV experts and scored based on the following criteria:

               • expected impact on the HIV cure field
               • appropriateness of the proposed work with respect to allotted funds
               • competency and track record of members of the team

3. Applicants with the highest-scoring LOIs that meet amfAR funding priorities are invited to submit full applications. Full applications are reviewed by members of amfAR’s Scientific Advisory Committee and discussed during an in-person meeting to assess the merit of each application with respect to:

               • expected impact on HIV cure
               • innovation and novelty of the proposed work
               • competency and track record of members of the team
               • possible scientific or budgetary overlap
         
4. Successful applications are chosen based on reviewer comments, scores, and on amfAR priorities.

Requesting LOI Application Forms and Credentials

Submission of Letters of Intent is a two-step, online process.

1. REGISTRATION DEADLINE PASSED.

2. CLICK HERE to request log-in credentials. Username, password and a link to the submission portal will be sent to the email address provided.

3. Use the log-in information to complete and submit the LOI online through the portal. LOIs must be submitted via the portal no later than 3:00 p.m. EST on Tuesday, January 28.

Please be sure to request credentials and forms with adequate time to prepare a Letter of Intent. Deadline extensions will not be provided.

Other Important Dates (all dates are tentative)

Letters of Intent due: January 28, 2020
Invite full applications: February 14, 2020
Full applications due: April 17, 2020
Performance period begins: July 1, 2020