By Iana Seales
in Vienna, Austria
A clinical trial out of South Africa has provided ground-breaking evidence that the use of an anti-retroviral drug in the form of a vaginal gel can prevent HIV infections in women, but there are no immediate plans to roll out the product.
The results of CAPRISA 004, the most recent study on the efficacy of microbicides were
released at the AIDS 2010 conference in Vienna, Austria yesterday and the trial reported that after one year of use, there were 50% fewer HIV infections among women who used tenofovir gel compared to women who used the placebo gel during sex acts.
Dr. Salim Quarraisha Adbool Karim of the Centre for the AIDS Programme Research in South Africa (CAPRISA) called it an important study, but he also cautioned that confirmatory trials would need to be conducted before the gel is approved for use in countries across the world. His wife, Dr. Quarraisha Karim was the other key researcher on the project.
Dr. Karim was clear on the fact that more research is needed on microbicides, including studies of different dosing strategies, different formulations and products containing other antiretroviral compounds in order to confirm and preferably improve the level of effectiveness observed in CAPRISA 004. But they also reported that if the protective effect shown in CAPRISA 004 is confirmed by another study, the broader use of tenofovir gel could save millions of lives, especially in sub-Saharan.
Researchers have long searched for an effective microbicide which could add an important new strategy to HIV prevention efforts and scale up the treatment available to women everywhere including Commercial Sex Workers (CSW) who are often not in a position to negotiate condom use. The results of the trial were met with much enthusiasm yesterday; many in the massive audience present for the announcement stood up and applauded the scientists behind the study.
Tenofovir gel contains a well-known antiretroviral (ARV) drug called tenofovir that prevents HIV from replicating inside cells; it was first tested in monkeys before women were asked to participate in the study. The study involved 889 rural and urban South African women (ages 18 to 40 years) who were sexually active and HIV negative.
Dr. Quarraisha Kalim emphasized that the participants were provided with varying methods of prevention including condoms, and also the gel. The study found that after 30 months of gel use, women who used tenofovir gel had 39 percent fewer HIV infections compared to women who used the placebo gel during sex acts. The lower level of effectiveness in the second year of the trial was associated with less use of the gel by women who became infected with HIV.
According to the study, tenofovir gel was most effective when the participants adhered to the prescribed dosing regimen: Each woman was asked to apply a first dose of the assigned study gel within 12 hours before anticipated sexual intercourse, and to insert a second dose as soon as possible after intercourse. No data was available yesterday that indicates whether the gel has the same effectiveness if it is applied a short while before sexual intercourse.
Tenofovir gel was reported to be 54 percent effective among women who adhered to the dosing regimen at least 80 percent of the times they had sexual encounters; 38 percent effective among women who adhered to the regimen from 50 percent to 80 percent of the times they had sex; and 28 percent effective among women who adhered to the regimen less than 50 percent of the times they had sex.
The CAPRISA researchers also found that the effectiveness of the gel declined after the first 18 months of gel use in the study as the amount of gel being used by the participants decreased. 98 participants became HIV positive during the study.
Tenofovir was developed by Gilead Sciences and CAPRISA 004 was the first clinical trial to study and demonstrate the efficacy of a next-generation microbicide designed to prevent women from acquiring HIV through sex with an infected male partner.
In addition to showing efficacy against HIV, CAPRISA 004 found evidence that tenofovir gel also prevents transmission of herpes simplex virus type 2, or HSV-2. HSV-2 is a lifelong and incurable infection that can make those infected with the virus two-to-three times more likely to acquire HIV. Data collected during the CAPRISA 004 study indicate that tenofovir gel provided 51% protection against HSV-2.
Administrator of USAID Rajiv Shah, in welcoming the results shortly after they were announced, described them as an important first step towards establishing the effectiveness of using antiretroviral drugs to prevent HIV infection. He announced that after the results are confirmed in an ongoing and similar study supported by the National Institutes of Health in the US Department of Health and Human Services as well as other studies, USAID will work with partners at the global and country levels to integrate the product into programs. “As a leader in implementation science, USAID will collaborate with PEPFAR, multi-lateral agencies and partner countries to ensure the full benefits of this advance reach vulnerable women and girls across the world, particularly those in low-resource settings,” he said.
Guyana is one of the many countries that benefit from the US President’s Emergency Plan for AIDS Relief (PEPFAR) programme and may therefore be able to tap into the gel.
Shah said USAID is proud to be the major funder of the first-ever proof of concept that a microbicide can effectively and safely reduce the transmission of HIV from men to vulnerable women. “An achievement of this magnitude could not have been possible without collaboration among governments, scientists, communities, and individual women at risk of HIV,” Shah said in the statement. “I am proud USAID is at the forefront of scientific innovation. CAPRISA 004 is a model for future research studies in which clinical trials will be led by in-country investigators backed up by the scientific and operational expertise of their US colleagues. This approach builds the research capacity of the developing world, contributes to sustainable health systems, and exemplifies how President [Barack] Obama’s Global Health Initiative intends to leverage technology and innovation to improve health around the world,” he added.
All volunteers to the study who tested HIV positive were provided care including ARV treatment at the CAPRISA clinics and women who became infected during the study were enrolled into CAPRISA studies and/or the CAPRISA AIDS treatment programme at their respective sites for ongoing care and support.
This study was jointly funded by the Governments of South Africa and the United States, through the Technology Innovation Agency (TIA) and USAID, respectively. USAID provided US$16.5M and TIA provided US$1.1M for the study. “USAID is proud to be the major donor of this first-ever proof of concept that a vaginal microbicide can effectively and safely reduce the risk of HIV transmission from men to vulnerable women. The success of the CAPRISA 004 trial perfectly complements the Global Health Initiative and our focus on women’s health, both in prevention and sustainable health delivery systems,” Shah stated.