Global Pulse Blog

Figure 1.

For the first time in the 15 year-long search for an HIV prevention method that women can control, a vaginal microbicide gel called Viread has been shown to decrease the risk of HIV infection by as much as 54%.  Even though the microbicide does not prevent transmission in every woman who uses it, this is the first promising tool that women are able to use without the cooperation of the male partner.  This is an important consideration most of the new HIV infections in women living in Africa were acquired through forced sex with infected men who refuse to wear condoms. Women and girls represent 60 percent of the 22 million people infected with HIV living in Africa.

The gel 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. The Bill Gates Foundation also helped fund the trial.

In the clinical trial, coordinated by scientists at the Centre for the AIDS Program Research in South Africa (CAPRISA), the use of the microbicide was compared to a placebo in a group totaling 889 women located in either the urban setting of Durban or the  rural setting of Pietermaritzburg in the KwaZulu-Natal province of South Africa.

The main active ingredient of Viread was a 1% vaginal gel formulation of the nucleotide reverse transcriptase inhibitor tenofivir. The pill form of tenofivir is already used in combination with other antiretroviral agents for the treatment of HIV and works  by slowing HIV’s spread through a patient’s body.  The secret to tenofovir’s success as a topical agent may be that it absorbs into the vaginal wall and into the cells targeted by HIV. Other gels have had to be sufficiently spread around and present in the vagina during intercourse in order to work.

Participants of the clinical trial were instructed to apply the gel 12 hours before and up to 12 hours after intercourse. Participants were told that the gel was experimental and were also counseled to use condoms or another means of HIV prevention. According to the trial results, when compared with the placebo group, women in the tenofovir group showed 39 percent fewer HIV infections. Within the tenofovir group, women who used the gel more than 80 percent of the time had 54 percent fewer infections than women who used the placebo gel .  For women who did not use the gel regulalrly ( less than 80 percent of the time) there was a 28 percent reduction.

Some theories as to why the gel did not perform better:

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.

For that reason, the researchers said, it’s impossible to say how much protection this microbicide might afford any woman.

“We can only approximate it,” said Salim Abdool Karim of the University of KwaZulu-Natal in Durban, South Africa, who helped lead the study. “What you see is a mixture of the efficacy of the product mixed with the ability to use the product. It is fundamentally dependent on human behavior.”

Other scientists speculated that some women who became infected despite using the tenofovir gel might have been exposed to men with very high HIV load (which occurs soon after infection).

“My most likely explanation is that you have to go up on the dose,” said Anthony S. Fauci, who heads the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. “You may have maxed out on 1 percent,” he said, meaning a more concentrated gel might produce greater protection.

Over the past 15 years, six other microbicides were tested in 11 clinical trials, with none showing a protective effect.  Previous gels relied on drugs that weren’t specifically designed to target HIV.

Another important finding in the trial was that the gel prevented the transmission of genital herpes (caused by the herpes simplex virus-HSV) by 51%.  A genital herpes infection increases the susceptibility to HIV infection because the HSV virus can cause open lesions to form.

If further development and testing continues to be successful, more potent formulations combined with marketing that makes the product more appealing to women could lead to increased prevention of HIV transmission.

A product could be ready as early as 2013 if the results are confirmed by a second study known as Voice that is enrolling patients.

Gilead, which donated the active ingredient in the gel, won’t participate in the commercialization of the product in developing nations. They are unsure of whether or not will market the gel in the U.S. and Europe. Conrad gave the rights to manufacture the gel to the government of South Africa to get the product to women in the country most affected by the disease as quickly as possible.

The findings of the study were described at the 18th International AIDS Conference in Vienna, Austria and the research article was published in Science magazine.

For More Info:

1. Sciencenews
2. Businessweek
3. WashingtonPost