1% Tenofovir Gel for HIV Prevention

The Latest

• MTN Statement
• Questions and Answers document on DSMB decision (from MTN)
  
• AVAC Statement
• Listen to a recording of a global teleconference to discuss this development
  

Last updated November 25, 2011.

In January in Johannesburg, AVAC partnered with the Microbicide Trials Network (MTN), Southern African AIDS Trust and the Treatment Action Campaign to organize “Next Steps for ARV-based Prevention”, a civil society consultation on follow-up research with a focus on what may come after the VOICE trial. (VOICE is evaluating daily TDF, daily TDF/FTC and daily 1% tenofovir gel.) Given the recent results of the CAPRISA 004 microbicide and iPrEx PrEP trials, it is critical to continue to prepare for potential positive results from other ongoing trials of oral and topical ARV-based formulations.

Part of the civil society consultation was allocated to discussions of MTN 018, or CHOICE, a planned follow-on trial that would be initiated if one or more of the strategies being evaluated in the VOICE trial were found to be safe and effective. The forty advocates from East and Southern Africa discussed the proposed MTN 018 trial design as well as the regulatory process for approving the gel should it show effectiveness in VOICE—results are expected in early 2013. (The same gel candidate used in VOICE showed 39 percent protection against HIV in the CAPRISA 004 trial but used a different dosing strategy.) Following this community consultation, the MTN 018 Protocol Development Team met and incorporated the civil society feedback into its deliberations. Engaging civil society while the trial protocol is in development is an example of good participatory practice guidelines in action.

Background on 1% Tenofovir Gel

One percent tenofovir gel is a candidate microbicide currently being tested for its safety and effectiveness at reducing the risk of HIV infection in HIV-negative individuals who use the gel. The most recent data on the gel come from the CAPRISA 004 trial with nearly 900 women in Kwazulu Natal, South Africa [for more on CAPRISA 004, visit our trial webpage]. Results from this landmark trial were announced in July and showed the first ever positive effectiveness data for a microbicide. The trial found that 1% tenofovir gel reduced HIV-negative women’s risk of HIV infection via vaginal sex by an estimated 39 percent overall. The trial also found that 1% tenofovir gel reduced risk of HSV-2 infection by over 50% among women in the trial who were not infected with herpes simplex virus type 2 (HSV-2) at the beginning of the trial sex [ download the Science article that features the data set from CAPRISA 004].

While CAPRISA 004 was an important milestone in the search for an effective microbicide, it did not provide all of the answers needed to introduce use of 1% tenofovir gel as a new HIV prevention strategy. Additional research is needed to translate the CAPRISA 004 results into possible public health impact, and the potential designs for further studies are already being actively discussed. This expanded research agenda would complement the ongoing VOICE trial, which is testing once-daily dosing of 1% tenofovir gel along with two forms of oral pre-exposure prophylaxis (PrEP) in preventing HIV infections in Malawi, South Africa, Uganda and Zimbabwe. VOICE is a critical trial for learning more about both 1% tenofovir gel and oral ARV-based prevention, and it is critical to understand if regulatory bodies will consider results from this trial as a possible confirmatory trial of CAPRISA 004.

There have been a number of follow-up discussions regarding next steps for 1% tenofovir gel (see previous Advocates’ Network updates from August 24 and September 20), and AVAC will continue to monitor these developments as they unfold.

Essential reading:

• FDA and CONRAD Chart U.S. Regulatory Path for 1% Tenofovir Gel for HIV Prevention meeting report (October 25, 2010)
  
• UNAIDS Press Release (September 3, 2010), Road-map agreed for confirmatory trials of promising microbicide
• Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women, data published in Science (September 2010)
• Tenofovir gel clinical studies summary (August 25-26, 2010)
  
• A Cascade of Hope and Questions Vol. 2: Understanding the Results of CAPRISA 004 (August 2010)
  
• A Cascade of Hope and Questions Vol. 1: Anticipating results of ARV-based HIV prevention trials (July 2010)
• What do we know about tenofovir gel? Completed Safety Studies (August 2010)
  
• Do systemic and genital tract tenofovir concentrations predict HIV seroconversion in the CAPRISA 004 tenofovir gel trial? (July 2010)