Injectable Protects against HIV

Martina Kovarova, PhD

Martina Kovarova, PhD

Vaginal transmission accounts for the majority of new HIV infections worldwide. Pre-exposure prophylaxis, or PrEP, to prevent HIV transmission in the form of a vaginal gel and a vaginal ring has encountered poor efficacy in human trials due to problems with adherence. In an effort to minimize obstacles to adherence and prevent vaginal HIV transmission, researchers from Division of Infectious Diseases at the University of North Carolina School of Medicine and collaborators from Merck demonstrated the effectiveness of a new long-acting formulation of raltegravir in animal models. These results were published in the Journal of Antimicrobial Chemotherapy on Monday, March 21.

“Raltegravir is a well-tolerated drug with a strong track record of use for the treatment of HIV,” said Martina Kovarova, PhD, the study’s lead author, research assistant professor of medicine in the Division of Infectious Diseases at UNC’s School of Medicine. “Changing its form from an oral pill to a subcutaneous injection produced a long-acting release of the drug that can be used for pre-exposure prophylaxis.”

Kovarova and her team found that two weeks after a single injection of raltegravir, animal models had the same levels of the drug in their system as humans who take PrEP orally twice a day.

“We found that a single injection of a long-acting formulation of raltegravir resulted in strong suppression of viral load in both plasma and cervicovaginal lavages. We then evaluated this formulation of long-acting raltegravir in a validated model of vaginal HIV transmission. Our result show that long-acting raltegravir results in significant protection against multiple high dose challenges with highly relevant strains of HIV for up to 4 weeks (the last time analyzed in this study),” said Kovarova. “This means raltegravir has good penetration into the female reproductive tract, which has been a significant disadvantage of other drugs. It also means that an injection of long-acting raltegravir may only be needed every month or every few months to provide protection against HIV infection, which could improve adherence.”

“Effective long-acting formulations for HIV prevention represent the next-generation of pre-exposure prophylaxis. This is a very exiting new formulation of raltegravir with great potential,” said J. Victor Garcia, PhD, a co-author in the study and professor of medicine in the Division of Infectious Diseases at UNC’s School of Medicine.

This study was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.