Self-administrable inserts demonstrate high efficacy as topical on-demand pre- and post-exposure prophylaxis in macaques
Thanks to several key collaborations, researchers at CONRAD have achieved an important research and development milestone in the fight against HIV with an on-demand topical delivery system that significantly reduces the risk of becoming infected. An insert combining the potent antivirals tenofovir alafenamide and elvitegravir that may be used both vaginally or rectally has shown preclinical proof-of-concept with high efficacy against HIV in preclinical macaque models. The insert has also been tested in Phase I clinical trials, both vaginally, and rectally, with excellent results. This novel insert is a promising new HIV and genital herpes prevention method, all in a package that is ultimately meant to be discreet, portable, affordable, and which can be easily self-administered on demand.
On-demand topicals fill a critical gap in available products for PrEP users that might prefer occasional, infrequent product use over daily regimens or long-acting options due to specific lifestyles and patterns of sexual activity. The tenofovir alafenamide/elvitegravir insert will address this unmet need with a product that may be used either vaginally or rectally, either before sex or after as a “morning after” post-exposure prophylaxis. Tenofovir alafenamide and elvitegravir are both very potent antivirals that are parts of FDA-approved regimens for HIV treatment and/or prevention, with extensive preclinical and clinical data available.
The product development work thus far has mostly been funded by PEPFAR through cooperative agreements between USAID and CONRAD/Eastern Virginia Medical School. In collaboration with CONRAD, Gilead Sciences, Inc. has provided the tenofovir and elvitegravir drug substances to support the development of this product. Combining both of these drugs into a single on-demand topical delivery system yields a flexible product with high efficacy, able to both block HIV virus from replicating and from integrating into the DNA of a host cell. These continuing advancements are supported by ongoing partnerships with the Microbicide Trial Network (NIH/NIAID/DAIDS), Magee-Womens Research Institute, the University of Pittsburgh, The University of Alabama at Birmingham, the Statistical Center for HIV/AIDS Research and Prevention, FHI 360, and MATRIX, a program funded by USAID’s Office of HIV/AIDS..
TAF/EVG fast-dissolving inserts developed by CONRAD for on-demand HIV prevention were demonstrated safe and well-tolerated in the Phase I MTN-039 study, the results of which were presented at this year’s Conference for Retroviruses and Opportunistic Infections in Seattle:
The MTN-039 study was supported by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health of the U.S. National Institutes of Health.
Recently published clinical research from CONRAD’s own Phase I Study of the TAF/EVG inserts found them to be safe, acceptable, and satisfying PK/PD benchmarks for extended mucosal protection against HIV-1 and HSV-2:
These results showcase the promise of this high-efficacy insert with dual modalities for vaginal or rectal use as a topical on-demand option for HIV and HSV prevention. Already self-administrable before or after sex in a way that may better align with the differing needs of HIV prevention users compared to other existing products, the inserts have already completed first-in-human clinical trials in men and women using a single dose vaginally or single or double dose rectally. A planned clinical study MATRIX-001, a multi-vaginal-dose Phase I safety/PK/PD study to evaluate the urogenital and systemic safety of the TAF/EVG insert, will be conducted at the EVMS Clinical Research Center (US), CAPRISA (SA), and KEMRI (Kenya).
Product development and main studies were made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of CONRAD and do not necessarily reflect the views of USAID or the United States Government.