A microbicide gel containing Gilead’s HIV drug tenofovir used by women before and after sex has been shown to reduce their risk of HIV infection by nearly 40%, according to a study unveiled at the International AIDS Conference-AIDS 2010, Reuters reports (Ingham, 7/19).

The Centre for the AIDS Programme of Research in South Africa (CAPRISA) trial showed that the gel “curbed the risk of infection by the human immunodeficiency virus (HIV) by 39 percent overall, but by 54 percent among those women who used it most consistently,” Agence France-Presse reports (7/19). “The gel also reduced the risk of contracting genital herpes by 51 percent, a factor which could slow the spread of HIV even further, given that people with genital herpes have double the risk of getting HIV,” according to the study, HealthDay News/U.S. News & World Report writes (Gardner, 7/19).

“The clinical trial of the microbicide – a 1% concentration of the drug incorporated into a colorless, odorless gel and distributed in a plastic applicator – was organized by the husband-and-wife team of Dr. Quarraisha Abdool Karim and Dr. Salim S. Abdool Karim of the Center for the AIDS Program of Research in Durban, South Africa,” the Los Angeles Times reports.

As detailed in the study, published online Monday in the journal Science, researchers “enrolled 889 sexually active women between the ages of 18 and 40 in the South African province of KwaZulu-Natal; about half received the gel with microbicide and half a placebo. The women were told to use the gel in the 12 hours before they expected to have sex and in the 12 hours afterward. The researchers collected applicators to monitor compliance,” according to the newspaper (Maugh, 7/20).

“The gel [used in the trial] was developed by CONRAD, a nonprofit organization based in Arlington, Virginia, and funded by the U.S. and South African governments under royalty-free license from Foster City, California-based Gilead, the world’s biggest maker of AIDS medicines,” Bloomberg Businessweek reports in an article that looks at the future production of the microbicide (Randall/Bennett, 7/19).

The study “is the first time an HIV-prevention method controlled by women, who bear the brunt of the epidemic in Africa, has been shown to work. About a third of women in the study said their partners didn’t know they were using the clear, odorless gel,” the Wall Street Journal reports. “The findings come at a time when donor nations have been balking at continued large increases for funding AIDS treatment, intensifying pressure on finding new ways to prevent people from contracting the virus in the first place,” the newspaper adds (Schoofs/Wonacott, 7/20).

“Over the past 15 years, six other microbicides were tested in 11 clinical trials, with none showing protection,” the Washington Post reports (Brown, 7/19).

“All participants were tested for HIV at monthly follow-up visits, at which they also received reproductive health services, such as pregnancy tests, and HIV prevention services, including pre- and post-test counseling, HIV risk-reduction counseling, condoms and treatment for other sexually transmitted infections,” CBC News reports. “At the end of the study, there were 38 HIV infections among the microbicide group compared with 60 in the other group,” the news service adds (7/19).

“[W]hy the drug-containing gel did not work even better perplexed some scientists and will probably be a subject of more study,” the newspaper adds. “The net impact seen in the study reflects the combined effect of many variables, only one of them the action of tenofovir, which penetrates into the vaginal tissue, protecting the cells that HIV targets for infection. Other variables include the prevalence of HIV infection in the male population; the number of sexual partners a woman had; the amount of AIDS virus (‘viral load’) in an infected man’s semen; concurrent use of condoms; and, most important, the consistency with which a woman used the gel,” Washington Post writes.

“For that reason, the researchers said, it’s impossible to say how much protection this microbicide might afford any woman,” the newspaper writes. The article includes comments by Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), and other HIV/AIDS experts (Brown, 7/19).

More Trials Needed

“Broader trials are needed to confirm the results, and it will most likely be years before the product is publicly available, but if produced on a large scale the gel would cost less than 25 cents per application, the lead investigators estimated,” the New York Times reports. “Because the trial was relatively small and the gel was nowhere close to 100 percent effective, AIDS scientists and public health officials wanted to see another trial get similar results before they undertook the large fund-raising and public education efforts that would be needed to make billions of doses of the gel, as well as the applicators, which are more expensive, and then to persuade women to use them and governments of poor countries to adopt them” (Dugger, 7/19).

The Wall Street Journal also notes caveats to the study, including the fact “[t]he effectiveness of the intervention seemed to wane over time, dropping from 50% at one year to 39% at two and a half years” (7/20). “Rather than an issue with the medication, the researchers speculate that it was ‘largely due to diminishing adherence,’ Salim Abdool Karim said, noting that women might have come to internalize the disclaimers repeated at their monthly clinic visits – that the gel was only experimental and might not work at all,” Scientific American’s “Observations” blog reports (Harmon, 7/19).

“At 12, 18, 24 and 30 months, the gel showed statistically significant protection against HIV. Still, the trial wasn’t designed to have enough statistical power to win regulatory approval for the gel, said Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, who wasn’t involved in the study. It is ‘a proof of concept that needs to be validated’ by a second trial, he said,” the newspaper writes. “A larger trial of about 5,000 women, using the same gel but with a different dosing regimen, is under way in Africa. Results aren’t expected until 2013” (7/19).

“[T]he gel still needs to be further researched, licensed and approved and is not likely to be available to women at clinics any time within the next year or two, said [Salim] Abdool Karim,” HealthDay News/U.S. News & World Report adds (7/19).

Still, HIV/AIDS experts gathered at AIDS 2010 expressed optimism in response to the study, the New York Times continues. “This is very encouraging,” UNAIDS Executive Director Michel Sidibe said. “It can be controlled by women, and put in 12 hours earlier, and that is empowering. They do not have to ask the man for permission to use it. And the cost of the gel is not high” (7/19).

“In the study, each dose of the gel cost 32 cents, of which 30 cents went to the plastic applicator and packaging. Economies of scale would likely slash that price, and the drug itself would probably only cost a penny per dose, according to the Clinton Health Access Initiative,” the Wall Street Journal adds (7/20).

“Even partial protection is a huge victory,” according to the Associated Press/Philadelphia Inquirer and “[c]ountries may come to different decisions about whether a gel that offers this amount of protection should be licensed” (Marchione, 7/20).

“The CAPRISA 004 study is an exciting scientific achievement that moves us one step forward to gaining another effective tool to prevent HIV infection,” Fauci said in a statement. “However, because no one approach will be appropriate or acceptable to all, we must continue to pursue a range of HIV prevention modalities, including microbicides, PrEP, and vaccines, as we simultaneously pursue scientific strategies designed to bring us closer to finding a cure for HIV/AIDS” (7/19)

“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,” USAID Administrator Rajiv Shah said in a statement. Shah also noted that trials led by in-country investigators, “builds the research capacity of the developing world, contributes to sustainable health systems, and exemplifies how President Obama’s Global Health Initiative intends to leverage technology and innovation to improve health around the world” (7/19).

Meanwhile, Reuters reports that South African Health Minister Aaron Motsoaledi, who spoke Tuesday at the conference, said of the trial, “We believe in an evidence-based approach and if scientists say this thing is going to work, then we will definitely be looking at it. … So far, evidence is showing that it is … very promising.”

According to the news service, Fauci “said countries with the greatest need should be able to move forward with using new HIV/AIDS medicines without having to wait for regulators such as the U.S. Food and Drug Administration to license them. … He also said he could see no reason why … PEPFAR, would not be free to decide to pay for such a gel for the use in developing countries even before it gets approval from drugs regulators” (Kelland, 7/20).

A Reuters factbox highlights findings from the CAPRISA trial (7/19).

A Wall Street timeline explores scientists’ efforts to develop a gel capable of protecting against HIV, dating back to 1990 (7/19).

Webcasts of the trial presentation and press conference are now available.  All of the Kaiser Family Foundation’s webcasts of select sessions from AIDS 2010 are available at www.kff.org/aids2010.