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Published on: December 9, 2010
Hypo-osmolar rectal douche tenofovir formulation prevents simian/human immunodeficiency virus acquisition in macaques
Peng Xiao1, Sanjeev Gumber2, Mark A Marzinke3,4
1New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, Louisiana, USA.
Abstract:
In spite of the rollout of oral pre-exposure prophylaxis (PrEP), the rate of new HIV infections remains a major health crisis. In the United States, new infections occur predominantly in men having sex with men (MSM) in rural settings where access to PrEP can be limited. As an alternative congruent with MSM sexual behavior, we have optimized and tested tenofovir (TFV) and analog-based iso-osmolar and hypo-osmolar (HOsm) rectal douches for efficacy against rectal simian/human immunodeficiency virus (SHIV) infection of macaques. Single TFV HOsm high-dose douches achieved peak plasma TFV levels similar to daily oral PrEP, while other formulations yielded lower concentrations. Rectal tissue TFV-diphosphate (TFV-DP) concentrations at the portal of virus entry, however, were markedly higher after HOsm douching than daily oral PrEP. Repeated douches led to significantly higher plasma TFV and higher TFV-DP concentrations in rectal tissue at 24 hours compared with single douches, without detectable mucosal or systemic toxicity. Using stringent repeated intrarectal SHIV exposures, single HOsm high-dose douches delivered greater protection from virus acquisition for more than 24 hours compared with oral PrEP. Our results demonstrate a rapid delivery of protective TFV doses to the rectal portal of virus entry as a potential low-cost and safe PrEP alternative.
Insights
New rectal douches using tenofovir (TFV) offer a promising alternative to oral pre-exposure prophylaxis (PrEP) for preventing HIV. These douches deliver higher drug concentrations to the rectal tissue, providing significant protection against rectal SHIV infection in macaques.
Area of Science:
- Virology
- Pharmacology
- Public Health
Background:
- Despite oral pre-exposure prophylaxis (PrEP) availability, new HIV infections persist, particularly among men who have sex with men (MSM) in underserved areas.
- Limited access to oral PrEP in rural settings highlights the need for alternative HIV prevention strategies.
- Rectal exposure is a primary route for HIV transmission in MSM, necessitating targeted prevention methods.
Purpose of the Study:
- To evaluate the efficacy of tenofovir (TFV) and analog-based rectal douches as a potential alternative to oral PrEP.
- To assess the pharmacokinetic and safety profiles of iso-osmolar and hypo-osmolar (HOsm) rectal douches.
- To determine the protective effect of rectal douches against simian/human immunodeficiency virus (SHIV) infection in macaques.
Main Methods:
- Optimized and tested iso-osmolar and hypo-osmolar (HOsm) rectal douches containing tenofovir (TFV).
- Assessed TFV and TFV-diphosphate (TFV-DP) concentrations in plasma and rectal tissue after single and repeated douches in macaques.
- Evaluated the protective efficacy of TFV HOsm douches against repeated intrarectal SHIV challenges.
Main Results:
- Single high-dose TFV HOsm douches achieved plasma TFV levels comparable to daily oral PrEP.
- Rectal tissue TFV-DP concentrations were significantly higher with HOsm douching than with oral PrEP.
- Repeated douches increased plasma and rectal TFV-DP levels without observable toxicity.
- Single HOsm high-dose douches provided greater protection against SHIV acquisition for over 24 hours compared to oral PrEP.
Conclusions:
- Rectal TFV HOsm douches enable rapid delivery of protective drug concentrations to the rectal site of HIV entry.
- This rectal douche formulation demonstrates potential as a safe, low-cost, and effective alternative PrEP strategy for MSM.
- Further research into rectal douches could significantly impact HIV prevention efforts, especially in resource-limited settings.
