This update contains information on an upcoming advocates’ call scheduled for Friday, September 24, 10-11am ET to learn about and discuss proposed next steps for the development of 1% tenofovir gel as an HIV prevention tool. The call will be one of many opportunities in the next few months to discuss this key development in biomedical prevention research and the implications of these and other upcoming results. There are a variety of background materials online at avac.org/tenofovirgel, and some of the issues that we will be discussing on the call are described in more detail below. We hope you’ll join us! Click here to register for the call.
In a South African trial known as CAPRISA 004, 1% tenofovir gel reduced HIV-negative women’s risk of acquiring HIV infection by approximately 39 percent overall over 30 months. 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. The evidence related to HSV-2 is an additional exciting outcome from CAPRISA 004.
This landmark trial provided the first evidence that a microbicide can reduce women’s risk of HIV infection via vaginal sex. However, it did not provide all of the answers needed to introduce use of 1% tenofovir gel as a new HIV prevention strategy. Additional studies of tenofovir gel are already underway, 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.
It is now critical that these various studies be prioritized as part of a clear product development strategy that could lead to a submission for licensure to one or more regulatory bodies. This strategy must have clear timelines and budgets, and funders must commit the necessary financial resources to ensure this strategy is fully implemented as quickly as possible.
On August 25-26, UNAIDS and the World Health Organization, along with the South African Department of Science and Technology, convened a meeting with researchers, regulators, funders, civil society and policy makers to discuss next steps and priority research needed around 1% tenofovir gel given the positive CAPRISA 004 result.
This consultation was preceded by several civil society dialogues—including a Johannesburg forum attended by roughly 200 activists and advocates that was jointly organized under the umbrella of South African National AIDS Council by AVAC, the Reproductive Health and HIV Research Unit, the Treatment Action Campaign and the Global Campaign for Microbicides. A report from this meeting will be available shortly, along with a list of the many questions that were raised.
Proposals for Follow-up Research
In a subsequent September 3 press release, UNAIDS summarized the conclusions of the August 25-26 meeting and described two trials that could be conducted to add depth and detail to current data about 1% tenofovir gel. These proposed trials would complement the ongoing VOICE trial that 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. Discussions with regulators are ongoing about how data from VOICE and other proposed trials might contribute to regulatory decision making about 1% tenofovir gel.
One of the new trials is being planned by a consortium of leading South African researchers and would take place primarily in South Africa. It is being designed to test the same dosing strategy as CAPRISA 004 in women aged 16-30 years old in a variety of settings. It will also seek to establish the safety of the gel in sexually active 16 and 17-year-olds (enrolling women of these ages, who were excluded from CAPRISA 004), and gather more information on 1% tenofovir gel as a tool for preventing HSV-2 infection.
The other proposed trial is being developed by the Microbicides Development Programme and would be conducted in other African countries and would compare two different dosing schedules. One dosing schedule would be the CAPRISA 004 dosing regimen, where women following this regimen would be instructed to insert one applicator of gel as close to the time of sex as possible, but no more than 12 hours before, and one applicator within 12 hours after sex, with a maximum of two doses in 24 hours. The other dosing schedule to be tested would be single-use coitally dependent dosing, where women would be instructed to insert a single application of the gel before sex or, failing that, immediately after sex.
In addition to these proposed trials, there are also plans to conduct operational research in the communities where CAPRISA 004 was carried out. The details of this research are still being finalized, but the protocol will be designed to gather additional information on patterns of gel use among women now that there is initial evidence that 1% tenofovir gel reduces HIV risk. It will allow HIV-negative CAPRISA 004 trial participants to access the gel in the context of a research setting.
These proposed follow-up trials will complement additional planned and ongoing research looking at the safety and acceptability of 1% tenofovir gel in pregnancy, rectal use and other key topics.
Community Questions and Issues
The CAPRISA 004 result has sparked exciting conversations and numerous questions from communities around the world. Advocates have a critical role to play in both posing and shaping the answers to the questions below and others that may arise from conversations in the coming months.
Some of the questions are about plans for follow-up research. These include:
- Why, if the first trial showed effectiveness, is there a need for more studies?
- Why are the follow-up studies going to have a placebo arm (in which participants would receive an inactive gel that is identical to 1% tenofovir gel but does not contain tenofovir)?
- CAPRISA 004 took place only in South Africa, and VOICE is taking place in Malawi, South Africa, Uganda and Zimbabwe—what types of data will other countries require to make decisions about licensing the product?
- What might regulatory bodies actually require for licensing tenofovir gel?
- How should the various additional studies be prioritized and sequenced?
- What additional evidence is required for product licensure, compared to what additional evidence is required for optimizing future rollout of a product?
Other questions are focused on resources and leadership:
- What are the resources needs for a follow-up research agenda that can quickly and efficiently provide answers to key questions?
- Why is there an apparent funding shortfall at this critical juncture?
- Who should be paying for the next trials?
- Who is leading the development of a comprehensive plan tackling follow-up research and regulatory and manufacturing pathways?
- What about investments in other potential candidates?
- Is there anything that the microbicide field had been funding that it can now set aside, given the CAPRISA 004 result?
To discuss these issues and many more, please join AVAC and a panel of invited resource people for an open advocates’ dialogue on Friday, September 24, 10am ET (visit www.timeanddate.com for the time in your area). Please register for the call here--upon registration you will receive call-in details.
The call will include a brief overview of the current data, ideas for the way forward, and a facilitated discussion with key resource people. We don’t expect to answer all of the questions, but it is our hope to accelerate the dialogue in developing a clear path forward.
We’ll post a recording of the call on our website and summarize proceedings from this and other discussions in our materials in the coming months.
Looking forward to hearing your voice!