Media statement
Major Study Finds Tenofovir Gel has No Effect on HIV
No concerns for participants’ safety
DURBAN, 25 November 2011 – VOICE*, an HIV-prevention study to evaluate the effectiveness of two different antiretroviral (ARV) approaches – a tablet and a vaginal gel – will be dropping the gel from the study. This is because a routine review of study data concluded that the microbicide, tenofovir gel, was not effective in preventing HIV in the women enrolled in the trial.
The study was designed to evaluate both the safety and effectiveness of tenofovir gel when used daily. The gel was developed by Gilead Sciences and manufactured by CONRAD in the USA, and has been previously tested in the USA and Africa.
The Prevention Trials Data and Safety Monitoring Board (DSMB) of the US National Institute of Allergy and Infectious Diseases (NIAID), which conducted the review on 17 November 2011, identified no safety concerns in relation to daily use of the tenofovir gel.
“The DSMB reviewed the data which suggested that there was no difference in the effect against HIV between those receiving tenofovir gel compared to those who received the gel without tenofovir (placebo). The incidence or the number of new HIV infections among participants using the placebo gel was 6.1% per year and among those using the tenofovir gel it was 6.0%,” says Professor Gita Ramjee, co-investigator for VOICE and Director of the HIV Prevention Research Unit at the South African Medical Research Council (MRC). The MRC is one of five South African institutions (CAPRISA, Aurum Health, PHRU and WRHI) conducting VOICE. Other participating sites are in Zimbabwe and Uganda.
Community working group member, Rita Bajities, upon learning the results said, “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”.
Participation in HIV prevention trials is voluntary and all women are offered current prevention options such as safe sex counseling, treatment for sexually transmitted infections and condoms. However, many women are not always able to negotiate safe sex resulting in the risk of acquiring HIV infection.
A participant on the gel arm, Hloni, remarked, “Ha! 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 proud the study found something. I am disappointed but not discouraged”.
Professor Ramjee said women participating in the gel arm of the trial would go through the usual process of medical checks and tests as they exited the study. “Since there are no safety risks to our participants, the exit process will take place in the next few months during the participants’ scheduled clinic appointments in December 2011 and January 2012 at all participating sites.” All women are in the process of being informed at all sites. All key stakeholders in the community have been informed.
VOICE will continue the arm of the trial that focuses on testing the ARV tablet, Truvada. The trial will conclude in mid-2012 and the full set of data – including data on the gel – will be available several months later after study close out and analysis is complete. Only then will we be able to explain why tenofovir gel showed no effect on HIV in the VOICE trial.
When VOICE was launched in 2009, it set out to test three products. Oral tablets of tenofovir and Truvada respectively, against its matching placebo. In addition, the study also tested tenofovir vaginal gel against a placebo gel. The study was approved by the local ethics committee and the MCC in South Africa. A total of 5 ethical review boards (3 in South Africa) monitored the study conduct including safety outcomes. A total of 5029 women were enrolled. One thousand women were enrolled in the gel arm and 1000 in the placebo gel arm. In September 2011, the DSMB found that oral tenofovir tablet had shown no effect in preventing HIV and this arm of the trial was subsequently dropped and 1000 women participants exited the study. Similarly, 2000 women in the gel arms will now exit the study.
Last year, the CAPRISA (CAP004) trial, found that tenofovir gel was 39% more effective than a placebo gel in preventing HIV infection, with the possible effectiveness range falling anywhere between 6% and 60%. The number of women in the CAP004 trial using gel was 445. The number of women in VOICE using the gel was 1000. The CAPRISA trial was conducted in KwaZulu-Natal whereas the VOICE trial was conducted at multiple sites in South Africa and in Zambia and Uganda. The other difference in the 2 studies is that in CAP004 the women used the gel 12 hours before and 12 hours after sex but not more than 2 doses in 24 hours. In VOICE the women used the gel daily.
“Although it is disappointing that VOICE has shown the gel to be ineffective among the women who participated in this particular study, the information obtained adds a critical dimension to discussions about the future of tenofovir gel,” comments VOICE lead investigator Dr Zvavahera Mike Chirenje of the University of Zimbabwe in Harare. “VOICE has been a particularly large study, involving more than 5000 women in South Africa, Uganda and Zimbabwe. We are extremely grateful to all the women who have participated in VOICE. Their role in answering the scientific questions of HIV prevention is not diminished by the outcome of the oral and vaginal tenofovir arms.”
A third study to measure the efficacy of tenofovir gel in HIV prevention commenced in South Africa a few weeks ago and is expected to yield results in 2014. Known as FACTS 001, the trial is more similar in design to the CAPRISA 004 trial where women are requested to use the gel before and after sex. The study will be conducted regionally in SA.
The remaining arm of the VOICE trial, testing the efficacy of Truvada tablets, is also of particular interest because earlier studies on this product have yielded differing outcomes.
Two previous studies of Truvada, Partners PrEP and TDF2, found the tablet to be more effective than a placebo pill in preventing HIV infection. The participants in both these studies comprised both men and women. In Partners PrEP, as the name suggests, participants were couples with one HIV-positive and one HIV-negative partner and Truvada was found to be 73% more effective than a placebo in preventing HIV infection.
However, an all-female study of Truvada, FEM-PrEP, was not able to show that a daily dose of Truvada was effective in reducing HIV. While FEM-PrEP was in some respects similar to VOICE’s Truvada arm, the participants in FEM-PrEP were defined as women at higher risk of HIV-infection because they had multiple sex partners and/or engaged in sex frequently.
“Several studies are required to establish whether any medicinal intervention is effective. This is as true for microbicides and oral HIV prevention as it is for any other drug,” Professor Ramjee comments. “The need for more effective forms of HIV prevention – especially for women, who constitute 60% of people living with HIV – remains compelling. As researchers, we will take the VOICE experience on board to inform the future research agenda in the field.”
*VOICE stands for Vaginal and Oral Interventions to Control the Epidemic. It is a trial conducted by the Microbicide Trials Network (MTN) in the United States, an HIV/AIDS clinical trials network funded by NIAID, the Eunice Kennedy Shriver Institute for Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health. VOICE involves 15 trial sites in South Africa, Uganda and Zimbabwe and 5029 women as participants. The South African research organizations and research locations are: Medical Research Council (multiple sites in Durban), Centre for the AIDS Programme of Research in South Africa (Durban), Aurum Institute (Klerksdorp), Perinatal HIV/AIDS Research Unit (Soweto), and Wits Reproductive Health and HIV Institute (Johannesburg CBD).
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