Topical Agents to Prevent HIV Transmission

The race is on to develop a topical preventive agent for reducing the transmission of HIV. Researchers at the University of Texas report in vitro efficacy of a vaginal cream containing silver nanoparticles. Other researchers are already reporting favorable results in human studies of an antiretroviral-containing gel.

According to researchers at the University of Texas, a vaginal cream that contains silver nanoparticles inactivates HIV and prevents its transmission for up to 72 hours after application.¹

Two critical proteins, known as CD4 and GP120, work together to facilitate the entry of HIV into human cells. By attaching to these proteins, the silver nanoparticles may block HIV penetration into uninfected cells.¹

Humberto Lara Villegas—a nanoparticle delivery system expert at the University of Monterrey, Mexico—collaborated with researchers at the University of Texas to formulate the novel cream. So far, testing has been confined to in vitro samples of human tissue. Although the in vitro testing predicts efficacy in prevention of viral transmission, results have not been validated in human studies.¹

Often, the in vitro efficacy of a medication does not translate to clinical efficacy in humans. For instance, in the 1990s, investigators evaluated whether the spermicide nonoxynol-9 could reduce the risk of HIV transmission when applied vaginally before intercourse. Results of clinical trials found conflicting results: a 1998 metaanalysis of these trials revealed inconclusive results, but later research showed that nonoxynol-9 actually increases the risk of HIV transmission.^2,3 As a result, the FDA issued a warning and changed the labeling of nonoxynol-9—containing products.³

Other researchers are farther along in the effort to create a topical preventive agent to reduce the risk of transmitting HIV. Researchers in the United States and South Africa have already begun human clinical trials of a vaginal gel containing the antiretroviral tenofovir. Results of a pharmacokinetic study in 144 women across 7 research sites show that vaginal tissue concentrations of tenofovir exceed those attained with an oral dose of tenofovir by a factor of ≥130 (P <.001).⁴ Based on these results, researchers expect a gel delivery formulation of tenofovir to outperform oral medications, such as the antiretroviral combination tablet Truvada (emtricitabine/tenofovir disoproxil fumarate; Gilead Biosciences, Inc), which already has an FDA-approved indication for prevention of HIV infection when taken prophylactically.⁵

Although other researchers are farther along in the approval process for a topical preventive agent, the University of Texas researchers remain hopeful that the silver nanoparticle vaginal cream formulation will reduce viral transmission in human trials. Looking ahead to safety issues that may occur in clinical trials, no adverse events have been associated with the silver nanoparticle cream to date, but Villegas cautions that testing is still in a very early stage. Future research will allow scientists to assess the potential for adverse events.¹

The next stage of research will involve experimentation in humanized mice. Researchers also plan to evaluate the efficacy of the silver nanoparticle cream for reducing the transmission of human papilloma virus.¹

Reducing transmission of HIV is an important priority of a multimodal risk-reduction strategy to slow the spread of HIV. Given past experience with nonoxynol-9, it is important to be cautious when evaluating claims announced in the early stages of drug development. However, with several research groups working on a topical preventive agent, cautious optimism is not unfounded. Approval of a topical preventive drug to reduce the spread of HIV would represent an important advance in the control of the persistent, devastating effects of the HIV/AIDS epidemic.

References

• Business Standard. Now, vaginal cream to prevent HIV transmission. http://www.business-standard.com/article/pti-stories/now-vaginal-cream-to-prevent-hiv-transmission-114012900383_1.html. Accessed January 30, 2014.
• Cook RL, Rosenberg MJ. Do spermicides containing nonoxynol-9 prevent sexually transmitted infections? A meta-analysis. Sex Transm Dis. 1998;25(3):144-150.
• FDA. New warning for nonoxynol 9 OTC contraceptive products re: STDs and HIV/AIDS. http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm124023.htm. Accessed January 30, 2014.
• Hendrix CW, Chen BA, Guddera V, et al. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. Plos One. 2014;8(1):e55013. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055013. Accessed January 30, 2014.
• TRUVADA (emtricitabine/tenofovir disoproxil fumarate) [package insert]. Foster City, CA: Gilead Sciences, Inc; 2013.