A single dose of raltegravir in the form of a long-term injectable antiretroviral was effective in an animal study that looked at preventing vaginal transmission of HIV, according to a recent study published in the Journal of Antimicrobial Chemotherapy.

Martina Kovarova, PhD, Research Assistant Professor of Medicine at the School of Medicine at the University of North Carolina Chapel Hill and colleagues injected 7.5 mg of raltegravir in laboratory-bred, immunodeficient mice and 160 mg into rhesus macaques and noted that after 14 days, plasma levels equaled 400mg twice daily oral pre-exposure prophylaxis (PrEP) doses in humans.

In an interview with Infectious Disease Advisor, Dr Kovarova said: “our results and those from others indicated that mice and rats have higher clearance rates of antiviral drugs from plasma compared with dogs, macaques and humans. Therefore, a dose of long-acting raltegravir formulation that reaches effective levels of plasma raltegravir to prevent HIV transmission has to be evaluated.”


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“Our preliminary data in macaques suggest that a dose of long-acting raltegravir 10 times lower compared to the dose in mice is able to deliver a comparable amount of raltegravir in plasma of nonhuman primates. This makes the long-acting formulation of raltegravir a promising agent for pre-exposure prophylaxis,” she added in the interview.

An injectable would likely improve prevention efforts because of ease of use. “Adherence to PrEP strongly correlates with the level of HIV protection.” the researchers noted in the study.

Following the observation that raltegravir suppressed viral load in cervicovaginal lavages and plasma, Dr Kovarova and colleagues saw that the drug offered ample protection against several strains of HIV over a period of 4 weeks. It was highly effective in combating HIV in the female reproductive tract, an area has posed a problem for other prophylaxis methods.

Dr Kovarova told Infectious Disease Advisor that, “When taken consistently, PrEP has been shown to reduce the risk of HIV infection by up to 92%. However, PrEP is much less effective if it is not taken consistently. Long-acting injectable drug formulations, including long-acting raltegravir we describe in the Journal of Antimicrobial Chemotherapy, may offer another option for PrEP.”

The study was funded by the National Institute of Allergy and Infectious Diseases.

Reference

1. Kovarova M, Swanson MD, Sanchez RI et al. A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges. J. Antimicrob. Chemother. 2016; doi:10.1093/jac/dkw042