R01AI162246

Ultra-Long-Acting Polymeric Injectable Multi-Purpose Prevention Technology for Contraception and HIV Prevention - Project Summary

Globally, over 50% of those infected with HIV are women, and annually, ~50% of all pregnancies are unplanned. Therefore, there is a critical need to promote female-controlled methods of multipurpose prevention technologies (MPTs) and delivery strategies that can be disassociated from the sex act.

Injectable formulations are well tolerated by men and women, are efficacious for contraception, and have high patient acceptability and compliance. Innovations recently introduced into the field of systemic pre-exposure prophylaxis (PrEP) are long-acting (LA) formulations of antiretrovirals (ARVs) that stably release drugs over many weeks as nano-formulations and have activity in animal models of prevention and in humans. Currently, there are two different LA formulations being considered for HIV prevention: a LA form of rilpivirine (RPV/TMC278) and a LA form of cabotegravir (CAB/GSK744). Injections of these LA ARVs require a 4-week 'lead-in' regimen using oral cabotegravir or rilpivirine to fulfill current safety considerations as once injected, these agents have detectable levels for months and the drug cannot be removed or have its clearance accelerated.

Despite these advances in HIV PrEP, currently there are no LA injectable MPT formulations in development mainly because of limitations of current LA injectable formulations utilizing nanoparticle suspensions whereby two drugs cannot be combined into a single injection.

In this R01 grant and building on our existing data, we propose a comprehensive evaluation of a first-in-line injectable MPT that offers durable and sustained protection from HIV transmission, high efficacy of contraception, increased user compliance, and the ability to be removed in case of unanticipated adverse events or when considering discontinuation from the LA HIV PrEP and/or contraception.

We will achieve this goal by developing a liquid MPT formulation utilizing excipients that form a biodegradable depot after subcutaneous injection (in-situ forming implant (ISFI)). We propose a comprehensive evaluation of this novel drug delivery approach using a highly relevant macaque model of mucosal simian/human immunodeficiency virus (SHIV) as an invaluable preclinical tool to assess the efficacy of the ISFI against SHIV acquisition.

This cutting-edge combined approach will be utilized to evaluate the scientific premise of our proposal to investigate whether sustained protection against HIV acquisition and pregnancy can be achieved using a unique and highly innovative ultra-long-acting coitally-independent MPT ISFI formulation.

University Of North Carolina At Chapel Hill

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Chapel Hill, North Carolina 275996117 United States

Single Zip Code

Bioengineering Research Grants (BRG) (R01 Clinical Trial Not Allowed) (PAR-19-158)

Amendment Since initial award the total obligations have increased 414% from $727,053 to $3,740,241.