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Long-Acting Raltegravir Shows Promise in Protection from HIV

Long-Acting Raltegravir Shows Promise in Protection from HIV
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THURSDAY, March 31, 2016 (HealthDay News) — A long-acting formulation of the integrase inhibitor raltegravir can protect humanized bone marrow-liver-thymus (BLT) mice from high-dose vaginal HIV challenges, according to an experimental study published online March 21 in the Journal of Antimicrobial Chemotherapy.

Martina Kovarova, Ph.D., from the University of North Carolina at Chapel Hill, and colleagues administered long-acting raltegravir subcutaneously to BALB/c, NOD-scid-gamma, and humanized BLT mice and rhesus macaques. Raltegravir concentration was analyzed in peripheral blood and tissue. In infected BLT mice, suppression of HIV replication was assessed. To examine protection from HIV transmission in BLT mice, two high-dose HIV vaginal challenges were performed.

The researchers found that the plasma concentration of raltegravir at two weeks after a single subcutaneous injection of long-acting raltegravir in BLT mice and rhesus macaques was comparable to 400 mg administered orally, twice daily in humans. Three weeks after administration of long-acting raltegravir, serum collected from mice efficiently blocked HIV infection of TZM-bl indicator cells in vitro. In plasma and cervico-vaginal fluids of infected BLT mice, viral RNA was suppressed by administration of long-acting raltegravir. At one and four weeks after administration of a single subcutaneous dose of long-acting raltegravir, BLT mice were protected from two high-dose HIV vaginal challenges.

“These preclinical results demonstrated the efficacy of long-acting raltegravir in preventing vaginal HIV transmission,” the authors write.

Several authors are employed by Merck & Co., and have limited numbers of shares or options in the company.

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