A Single Dose of a MIV-150/Zinc Acetate Gel Provides 24 h of Protection Against Vaginal Simian Human Immunodeficiency Virus Reverse Transcriptase Infection, with More Limited Protection Rectally 8–24 h After Gel Use

The gel, which contains the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 and zinc acetate (ZA) in a 3% carrageenan (CG) gel, has shown great promise in preventing vaginal acquisition of simian human immunodeficiency virus reverse transcriptase (SHIV-RT) in a stringent macaque model. The gel was introduced atraumatically into the vaginal vault before or after challenge with 10^3 TCID50 SHIV-RT. The study examined the efficacy of a single vaginal dose of the MIV-150/ZA/CG gel, as well as the ZA/CG gel, after vaginal challenge. The results showed that a single vaginal application of the MIV-150/ZA/CG gel, but not the ZA/CG gel, 24 hours before challenge was as effective as repeated application. The gel provided 88% protection against vaginal SHIV-RT infection when applied 24 hours before challenge. The study also examined the efficacy of the MIV-150/ZA/CG gel after rectal challenge. The results showed that rectal application of the gel afforded limited protection against rectal challenge when applied 8-24 hours before challenge. However, the gel showed a trend towards reduced infection frequency when applied closer to the time of challenge. The study used a stringent macaque model to evaluate the efficacy of the MIV-150/ZA/CG gel. The animals were housed and cared for at the Tulane National Primate Research Center (TNPRC) in compliance with the regulations detailed in the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals. The animals were anesthetized with ketamine-HCl and received post-procedural analgesia for all procedures. The study used a combination of methods to evaluate the efficacy of the MIV-150/ZA/CG gel, including quantitative RT-PCR to measure viral RNA copies, nested PCR to evaluate PBMC DNA virus, and ELISA to monitor SIV-specific antibodies. The results showed that the gel provided significant protection against vaginal SHIV-RT infection, and may provide efficacy against rectal infection when used closer to the time of HIV exposure. The study suggests that the MIV-150/ZA/CG gel has great potential as a highly effective vaginal microbicide that can provide 24 hours of protection against vaginal SHIV-RT infection. The gel may also provide efficacy against rectal infection when used closer to the time of HIV exposure. Further studies are needed to confirm these findings and to evaluate the safety and efficacy of the gel in humans. The gel was stored at room temperature and used within 28 days of formulation. Gel viscosity and anti-HIV activity were verified for each lot prior to in vivo use. The study used a combination of methods to evaluate the efficacy of the MIV-150/ZA/CG gel, including quantitative RT-PCR to measure viral RNA copies, nested PCR to evaluate PBMC DNA virus, and ELISA to monitor SIV-specific antibodies.