This result was unexpected and contradicted an earlier trial of the same vaginal gel, called a microbicide, containing the antiretroviral tenofovir.
In the earlier CAPRISA trial, the microbicide was found to be 39 percent successful in preventing HIV infection.
However, the much bigger Vaginal and Oral Interventions to Control the Epidemic (VOICE) involving 15 research sites in South Africa, Uganda and Zimbabwe and over 5000 women, found that the gel had no effect on HIV.
The women in the trial, all HIV negative and in the twenties, were either given the tenofovir gel or a placebo gel, and were not told which gel they were getting.
However, in the VOICE trial the women used the gel every day whereas in the CAPRISA trial, the women used it before and after sex only.
‘The incidence of HIV ‘ that is, the rate of new infections ‘ among participants using the placebo gel was 6.1% per year and among those using the tenofovir gel was 6.0%,’ according to VOICE co-investigator, Professor Gita Ramjee.
The trial started in 2009, and involved over 4000 South African women.
On hearing that the trial had been stopped, a participant identified only as Hloni, said: ‘Oh my God. I truly believed in the gel. In VOICE we used the gel every day. I thought it will be even better. I am disappointed but not discouraged’.
However, Rita Bajities, who was also part of the trial, was reduced to tears: ‘I was so confident that the tenofovir gel was a very good ARV and was going to work. I feel very down now. For myself, I was going to use the gel as a lubricant also. If I was a scientist, I will have tears in my eyes as they have worked so hard and did so much. This is disheartening’.
Prevention advocacy group AVAC said at the weekend that VOICE would continue to test whether the ARV pill, Truvada, will have any effect on preventing HIV in women.
‘This is a blow to the HIV prevention field but is not the definitive answer about whether 1% tenofovir gel is an effective HIV prevention product for women,’ said Mitchell Warren, AVAC Executive Director. ‘New interventions are studied in multiple effectiveness trials for exactly this reason. CAPRISA 004, the first trial of 1% tenofovir gel, found effectiveness in women. VOICE found no effect. The FACTS 001 safety and effectiveness trial of tenofovir gel, which has just begun in South Africa and uses a different dosing strategy from VOICE, will provide additional information and hopefully clarity about the effectiveness of tenofovir gel.’
‘One immediate priority is ensuring that communities directly connected to planned and ongoing trials of tenofovir gel are informed and engaged with discussions about the way forward. Finding prevention options that work for women must remain a top priority, and there is still crucial investigation of tenofovir gel as both a rectal and a vaginal microbicide, which must continue,’ Warren said.
‘Based on the limited information available at this time, we simply don’t know whether the lack of effect was due to biology, adherence, both, or something else. This is one reason why the ongoing FACTS 001 trial, which is evaluating a different dosing strategy, with different adherence requirements, should continue,’ Warren said. ‘The concept of ARV-based prevention has been proven, but to meet the prevention needs of different populations we need the right drug at the right time in the right place. We hope that further research with tenofovir- and other ARV-based options will provide a range of new prevention options.’
The disappointing news from the VOICE trial is the latest development in a complex picture of what ARV-based prevention means for HIV-negative women. ‘We must, without any delay, accelerate the development of prevention strategies for HIV-negative women that address possible adherence issues. While we do not yet know the role that adherence to the drug regimen might have played in the FEM-PrEP and VOICE trial data to-date, we know that, for some women, strategies that require less-frequent dosing, such as a vaginal ring inserted monthly, and long-acting injectables, will be simpler to use from an adherence stand point,’ Warren said.
‘Medical research is often complicated, and we know to expect setbacks along the way. But with 2.7 million new HIV infections every year, it is imperative that we continue to look for new ways to curb the epidemic,’ Warren added. ‘It is especially important that we focus on interventions that will help young women’who so often bear the brunt of the epidemic’protect themselves.’
‘There will never be a silver bullet for HIV prevention, so we must continue to rapidly expand testing, treatment and voluntary medical male circumcision, amongst the array of evidence-based interventions, while also accelerating the research and development of additional new options, notably a range of ARV- and non-ARV-based prevention methods and vaccines to protect against HIV.’