Advanced Platforms for HIV Viral Load Testing at the Point-of-Care

Overview

According to the FY 2021-2025 NIH Strategic Plan for HIV and HIV-Related Research coordinated by the NIH Office of AIDS Research (OAR), HIV persists as one of the world’s most serious public health, development, and economic challenges. New infections continue to devastate communities and destabilize crucial socioeconomic infrastructure around the world. In 2018, an estimated 37.9 million people worldwide were living with HIV, an increase of more than 12 percent from 33.4 million people in 2010.

Further, at the end of 2016, approximately 1.1 million adults and adolescents were living with HIV in the United States. About 15 percent of these were unaware of their HIV status. Of those who were aware of their HIV infection, only 63 percent were engaged in care, only 49 percent of those were retained in care, and only 51 percent of those in care achieved viral suppression. The low rates of treatment and viral suppression are alarming, especially given the overwhelming evidence from National Institutes of Health (NIH)-funded clinical trials in multiple settings that antiretroviral therapy (ART) enhances health and quality of life and that durable viral suppression virtually eliminates the risk of sexual transmission of HIV.

As reviewed by McFall et al. (Current Opinion in Biomedical Engineering 2019, 11:9–15), HIV viral load (VL) monitoring is generally performed at treatment initiation, then again after three to six months of ART, and at least once annually when VL is undetectable. Clinicians often check after one month of treatment to evaluate for alpha decay of the virus on therapy and to assess early adherence.

Since monitoring VL detects treatment failure and any detectable VL may result in sexual transmission of HIV, VL monitoring plays an important role in monitoring response to ART and assessing the potential for sexual transmission; i.e., infectiveness. However, there is a significant unmet need across the U.S. to provide VL testing at the point-of-care with a platform that is sufficiently sensitive and simple to use so that People Living with HIV (PWH) can be readily monitored in the clinic for response to ART and infectiveness.

Therefore, the National Institute of Biomedical Imaging and Bioengineering (NIBIB) announces that its Point-of-Care Technology Research Network (POCTRN) is soliciting proposals to further advance HIV viral load detection technologies in order to fill specific unmet national and global needs. Under this solicitation, NIBIB is seeking proposals to accelerate the validation and prototyping of innovative HIV VL testing platforms that are designed for use at the point-of-care that fill unmet national and global needs with a level of analytical performance, especially for VL limit of detection, that facilitates monitoring PWH on ART and accurately assessing infectiveness. Proposed solutions with optimized design, performance, and sample collection for infants are welcome but not required, as are platforms that employ innovative sampling methods.

POCTRN has assembled a national network of expert technical, clinical, manufacturing, and regulatory advisors who will provide individualized assistance for funded projects. Funding for projects selected for this program will be dependent on successfully meeting project milestones. NIBIB will provide in-kind support to accelerate projects that successfully meet milestones.

Submission Process

Submissions will follow a staged review process

Project proposals will be accepted and reviewed through POCTRN's application portal. Innovators can access the portal here.

To register, applicants must establish an account in the portal. Once registered, applicants will be asked to provide a submission Title and Executive Summary, the latter of which should include a brief description of the technology and how it will improve viral load testing at the point-of-care for PWH. Do not include any proprietary or confidential information in the Title and Executive Summary sections as they may be publicly shared if selected. Applicants will then need to respond to a series of specific prompts across different evaluation criteria that will include details of technical capability and readiness, clinical impact, commercialization pathway, and regulatory feasibility.

Applications must respond to all the following:

• Detail the limitations of the currently available solutions and describe how the proposed approach will advance upon current technology.
• Clearly define the current state of the art and highlight how the proposed technology will advance patient care and be adapted to the workflow at the point-of-care.
• Include data showing proof of concept of the proposed solution.
• Detail the advantages of the proposed solution, i.e. how the assay will be able to detect any major circulating HIV types in the target population with high specificity. For monitoring viral suppression, the assay should appropriately consider the need to prevent the detection of cell-associated HIV DNA and RNA.
• Demonstrate consideration for the cost of goods for the platform and suggest whether it appears feasible that the diagnostic test could be implemented at the point-of-care.
• Describe sample prep and processing from whole blood or plasma and how the technology can achieve detection limits approaching 1000 c/ml or better.

Responsive applications may also pivot and refine existing technologies toward new intended use at the point-of-care. Applicants with technology that could eventually be adapted for home use are strongly encouraged to apply. Multiple awards based on merit and portfolio diversity will be considered; anticipated budgets between $200-$500K, appropriate and justified for the proposed project, are expected.

Applications will NOT be considered for:

• Device technologies that do not significantly advance upon the state of the art.
• Animal model development: all in vivo models must be well established and characterized, and available to the applicant.
• Efforts to develop technology for fundamental study of HIV.
• Fundamental/basic research projects.
• Device technologies not regulated by the FDA.

Review process

Proposals will be reviewed by an external panel of experts for technical, clinical, commercialization and regulatory feasibility based on the Project Review Criteria stated below. NIH will make the final determination about which proposals will advance to the “deep dive” review stage for work package development based on stated criteria and potential for commercialization.

Projects selected for further consideration will be assigned a team of healthcare commercialization and subject matter experts to do a “deep dive” review into the project with the applicants. Depending on the maturity of the proposed project, this fast turn-around process will take from a few days to two weeks. The deep dive review will identify key risk factors that may impede the validation and prototyping of the proposed solution, as well as ways to mitigate these risks. In addition, the team will identify additional resources needed to accelerate the project.

The product of this planning will be a proposed work package for the performance period that will be reviewed by an external panel of experts for technical, clinical, commercialization and regulatory feasibility based on the Project Review Criteria stated below. NIH will make the final determination about which proposals will advance to the work package stage, with funding provided by a POCTRN Center and approved work beginning as soon as possible.

The work package will cover the full range of activities needed to validate and prototype the technology so that project teams will be in a competitive position for further funding from other sources after the performance period.

The deep dive team will continue to support funded projects, and NIBIB and POCTRN will provide milestone-driven financial and in-kind resources to maximally accelerate progress. NIH will closely monitor progress in the work package, assess milestone achievements, and evaluate the need for continued funding.

Project Review Criteria

Each application will be reviewed by an independent external expert panel to assess the potential of the proposed solution to meet each of the following criteria.

• The technology fulfills an unmet national and global testing need (as described above), including how the approach improves upon the state of the art.
• The technology is at a proof-of-concept stage at a minimum with preliminary data indicating feasibility so that the technology prototype can be independently validated during the performance period or is a platform that can be pivoted to HIV viral detection.
• Ability of the solution to serve/deploy to underserved, hardly-reached communities.
• The team has the skills and experience to advance the technology toward commercialization.
• The projected cost for the platform will not be a barrier to its implementation at the point-of-care.
• Price of the proposed product is competitive with alternatives and aligned with reimbursement.
• Viable plans are provided for eventual production including forecasts, timeline, milestones, supply chain needs, product cost, and other ramp-up considerations.
• The applicant demonstrates plans to establish a Quality Management System if not currently completed.
• Critical commercial partners, contractors, vendors, and service providers have been identified or secured.
• A viable regulatory outline is provided, inclusive of clinical studies plan.
• Appropriateness of the platform for CLIA waiver and implementation into a clinical workflow at the point-of-care. 

Timeline

Applications were due December 1, 2022, 11:59pm ET and no additional applications will be accepted.

It is anticipated that proposal review will occur in January 2023 with one or more awards being made shortly thereafter.

Award Information

Awards are expected to be up to approximately $500,000 total cost for one year. Budgets should cover the costs of platform validation and prototyping. Awards are milestone-based and selected teams must work collaboratively with assigned POCTRN experts and associated web-based tools, including the CIMIT's GAITS platform to continue. Full Federal overhead rates apply.

The deadline for this opportunity has passed.

FAQ

For other programmatic or technical questions please contact admin@poctrn.org.

About Point-of-Care Technology Research Center (POCTRN)

The goal of POCTRN is to develop technologies with clinical applications using a network model that enhances complementary strengths and builds multidisciplinary partnerships. NIBIB created POCTRN in 2007 to facilitate the development of a pipeline of point-of-care technologies with commercialization potential, to utilize a center structure that enables the incorporation of clinical and user needs in the development process, and to provide expertise and resources to address early barriers to commercialization and implementation.

About National Institute of Biomedical Imaging and Bioengineering (NIBIB)

The mission of NIBIB is to improve health by leading the development and accelerating the application of biomedical technologies. The Institute is committed to integrating the physical and engineering sciences with the life sciences to advance basic research and medical care.