Development of an ultra-long-acting, self-administered, dolutegravir-based treatment regimen for HIV-1 and HIV-HBV CO-infection

The National Institute of Allergy and Infectious Diseases awarded Exavir Therapeutics Inc. $998,034 on August 4, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop ultra-long-acting, self-administered dolutegravir-based treatment regimens for HIV-1 and HIV-HBV co-infection.

Exavir is optimizing aqueous formulations of dolutegravir and tenofovir prodrugs suitable for low-volume intramuscular and subcutaneous injection, scaling up the manufacturing process, and demonstrating in vivo proof of concept toward the desired target product profile. The work includes achieving readiness for GMP manufacturing and IND-enabling GLP toxicology studies. The project addresses gaps in currently available long-acting antiretroviral regimens, including limited treatment options for patients with HIV-HBV co-infection, resistance liability of existing agents, and lack of single-injection or self-administered regimens that facilitate patient adoption and adherence.

The award is structured as a Phase II SBIR project. Performance occurs in San Francisco, California, with a period of performance through July 31, 2029.

Abstract

Despite progress in long-acting (LA) antiretrovirals (arvs) for HIV treatment in recent years, there remains a significant unmet need for additional and better LA arvs antiretrovirals for patients, including key patient populations and market segments that will remain underserved. First, the only available LA complete treatment regimen and is comprised of suboptimal arvs with lesser potency VS. Guideline-preferred oral-only agents. Second, cabenuva requires intramuscular (IM) dosing administered by healthcare providers every one or two months, more frequently than the typical clinic visit schedule for plwh on a stable treatment regimen. Third, HIV-1 is more susceptible to developing primary drug resistance to CAB and LEN compared to guideline- preferred oral-only agents. Fourth, none of the approved or publicly announced investigational LA or ULA agents can treat HIV/HBV CO-infection. Last, there are no available single-injection or self-administered LA regimens to facilitate patient adoption, satisfaction, and long-term adherence to therapy. Exavir therapeutics, INC., is developing aqueous formulations of dolutegravir and tenofovir prodrugs suitable for low-volume intramuscular and/or subcutaneous injection(s). These formulations would represent a major leap in patient convenience and experience, advance the adoption of long-acting treatments, and improve tolerability and outcomes in patients with HIV and HIV/HBV CO-infection. We propose a direct-to-phase II sbir project to optimize the formulation of our drug product, scale up the manufacturing process of our product, and demonstrate additional in vivo proof of concept for the drug product towards the desired target-product-profile, and achieve readiness for GMP manufacturing and IND-enabling GLP toxicology studies. Upon the completion of the project, exavir will establish proof-of-concept necessary to move this novel treatment regimen towards phase 1 clinical trial.