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February 28, 2011

Post-Exposure Topical Vaginal Gel Containing Raltegravir Protects Macaques from SHIV Infection

Current prevention strategies for topical prophylaxis with gels containing reverse transcriptase (RT) or entry inhibitors that work early in the viral lifecycle may be more suitable for pre-exposure prophylaxis (PrEP) than post-exposure prophylaxis (PEP). Integrase inhibitors (INI) that block strand transfer work late in the virus lifecycle and mat be more suitable PEP. In light of this hypothesis and the cost limitations of PrEP, data looking at integrase inhibitors (INI) for use in topical gels for PEP was presented at the 18h Conference on Retroviruses and Opportunistic Infections in Boston today.

Charles Dobard from the CDC in Atlanta, GA presented information regarding the use of raltegravir (RAL) gel for use as a PEP agent. Pigtail macaques were vaginally challenged twice weekly with low dose SHIV inoculum followed by application of either placebo or 1% RAL vaginal gel 3 hours post challenge. Challenges were repeated twice weekly for up to 10 weeks.

Previous in vitro data had determined that RAL inhibition of SHIV lifecycle occurred up to 8 hours post-infection compared with RT gels which maintaned inhibition up to 2 hours post infection. Therefore, application of the RAL gel at 3 hours was expected to be within the inhibition period of the INI, but outside the inhibition period of an RT.

Six macaques underwent application of RAL gel 3 hours post challenge and 4 macaques received placebo. All 4 placebo subjects were infected with SHIV while only 5 of 6 were infected in the RAL gel group. The breakthrough-infected macaque was infected with wild type virus. Acute plasma viremia was blunted in the infected RAL macaques as was vaginal shedding, but there was no RAL drug resistance mutation noted during acute seroconversion.

These data support further investigation of INI for topical PEP as a female controlled modality with a longer post-exposure window of activity.

Dobard C, Sharma S, Parikh U, et al. High Protection against Vaginal Infection in Macaques by PEP with Gel Containing RAL. Presented February 28, 2011, at 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA. Oral Abstract 30.

Source: Reporting from Boston for PRN News: A.C. Demidont, DO