Microbicide Trials Network

July 19, 2010

Dear MTN Family and Friends:

The results of the first tenofovir gel study designed to test whether its use could prevent HIV in women,  CAPRISA 004, were to be announced in Vienna at the International AIDS Society (AIDS 2010) meeting tomorrow (July 20) by our colleagues Quarraisha and Salim Abdool Karim, along with a rapid online publication by the journal Science (http://sciencemag.org/). Given that a news organization has broken the embargo, Science and AIDS 2010 have agreed to release the results now.

There is good news. These results have brought us what we have long hoped for and all along believed in our hearts and minds was possible – proof of concept that a topical product can interrupt HIV transmission in women. Today marks a major turning point in our efforts to prevent HIV.

The study found tenofovir gel used in a dosing regimen timed before and after sex reduced HIV infections by 39 percent, a finding that is statistically significant and is sure to elicit excitement among the community of people engaged in HIV prevention research globally. Additional materials are attached that provide further information about these exciting results. 

The study also indicated that use of the gel reduced the risk of herpes simplex virus 2 by 51 percent among women participating in the trial. an interesting observation that will be important to investigate further.

We want to congratulate Quarraisha and Slim and the entire CAPRISA team on this remarkable achievement, for invigorating an entire field and giving women real hope of having an effective method that they can control. The study was conducted in exemplary fashion at every step of the way. CAPRISA 004 was a double-blind, randomized controlled trial that enrolled 889 HIV-uninfected women at two sites in urban and rural KwaZulu-Natal, South Africa. The trial started in late May 2007 and enrollment was completed in early January 2009. Study exit visits were completed at the end of November 2009. Women were on product on average 18 months and study retention was 95.2 percent. While the overall reduction in HIV risk was 39 percent, there was a trend toward higher effectiveness – a 54 percent reduction – among women who reported the best adherence to product use. Analyses for safety identified no significant concerns. The vast majority of the participants (97.4 percent) found the gel acceptable.

Not only has CAPRISA 004 raised the bar for VOICE, but the study has brought us to a critical crossroads where the responsibility is clearly ours to answer among the most vitally important questions in HIV prevention, particularly in women. VOICE will tell us about the safety and efficacy of daily use of tenofovir gel, information that will serve to complement CAPRISA’s study. While a statistically significant reduction of 39 percent is an outstanding result, many of us hold the hope that more frequent daily dosing could provide an even higher level of effectiveness. Moreover, the oral arms of VOICE will tell us about safety and efficacy of daily use of the ARVs tenofovir and Truvada. We have taken pride in VOICE’s unique design. Now, with the results of CAPRISA 004, there should be no doubt that VOICE is more relevant than ever. Continuing the study to completion is essential to corroborate CAPRISA’s findings and to obtain the level of evidence to support the possible licensure and widespread use of any of these approaches. We have nearly 1,000 women now enrolled in VOICE and 15 of 16 sites screening or enrolling participants. Our colleagues in Blantyre, Malawi, just completed a week of study implementation training. We are well on our way.

We hope to engage in any discussion about product availability and carefully consider –  in partnership with our clinical trial sites and communities – any implications for VOICE.  Typically, availability of a new drug within a country depends on regulatory approval and scaled-up production and distribution. These steps usually take several years after effectiveness has been confirmed. 

The VOICE team will be represented in a stakeholder meeting being convened by WHO and UNAIDS  in South Africa in the near future to discuss next steps with tenofovir gel.

CAPRISA 004 has given rise to a new HIV prevention landscape. It has given us hope and inspiration that the time will come when we have multiple tools and approaches that can be used by men and women at risk of HIV to reduce their risk of infection. But, our friends and colleagues, we must work harder than ever before to realize the promise. All eyes will be on VOICE and we must renew our resolve to implement this study with the highest level of study conduct and to complete the study as soon as possible. We can do it.

On behalf of the entire MTN family, we want to thank and congratulate the CAPRISA team for their important contribution and for leading the way for VOICE and other HIV prevention trials.

With great joy and hope,

Sharon Hillier and Ian McGowan