At Last, Vaginal Gel Scores Victory Against HIV
(Jon Cohen - Science
23 July 2010)
Goooooal! While South Africa was in the spotlight for hosting the World Cup games, its AIDS researchers were quietly preparing for an announcement of a major milestone in their fi eld: For the fi rst time ever, a vaginal gel has unequivocally blocked the trans mission of HIV.
In a trial that involved nearly 900 South African women, those who received a vaginal gel that contains an anti-HIV drug had a 39% lower chance of becoming infected by the virus than those who received a placebo. “It is the fi rst time any biological intervention against HIV-1 transmission has ever shown convincing effi cacy in a large trial,” says John Moore, who studies similar vaginal microbicides at the Weill Cornell Medical College in New York City. “It’s a clear-cut result with obvious protection at a meaningful level.”
More than 30 randomized, controlled studies of microbicides, vaccines, and drugs to date have failed to thwart sexual transmission of HIV or have yielded such marginal success that researchers wound up hotly debating the data for years after the trials were complete. But there’s no ambiguity about the data from this new microbicide study reported online in Science this week (www.sciencemag.org/cgi/content/abstract/science.1193748) and in a presentation at the 18th International AIDS Conference in Vienna: Of the 444 women who received a placebo gel, 60 became infected with HIV versus 38 infections in the 445 women who received the microbicide.
The result was statistically significant, and no serious side effects occurred. “It’s a moment we’ve been waiting for 2 decades,” says epidemiologist Quarraisha Abdool Karim, who, with her husband, Salim Abdool Karim, headed the study, known as CAPRISA 004.
The study began in May 2007 and enrolled sexually active women between the ages of 18 and 40 who attended clinics in KwaZulu-Natal, South Africa, an area that has an extremely high rate of new HIV infections in young females. Researchers randomly assigned the women to receive either an inert gel or the gel mixed with the anti-HIV drug tenofovir for 30 months. Participants were asked to insert the gel within 12 hours before and after having sex. They were also provided with condoms and HIV-prevention counseling.
The women reported their sexual activity each month, and the researchers also collected used gel applicator —181,340 to be exact—to monitor adherence. On average, women used the gel as advised nearly threefourths of the time. Subset analyses showed, as expected, that the women who used the gel most frequently had the most protection: In a group of 336 “high adherers” who used the gel as advised more than 80% of the time, the reduction in risk of infection over 30 months jumped from the 39% found in the entire group to 54%. In the group that used the gel less than half the time, the risk reduction plummeted to 28%. The study also found that adherence dropped over time; among the entire group, the gel reduced the risk of infection by 50% over the first 12 months versus 39% over 30 months. “Task number one is better adherence,” says Salim Abdool Karim, also an epidemiologist and the head of the Durban, South Africa–based CAPRISA, which stands for Centre for the AIDS Programme of Research in South Africa.
Both the CAPRISA investigators and other researchers who
were not involved with the study stress that these results do not
mean that a tenofovir microbicide gel is ready for
market. “It's a really exciting first step,” says Sharon Hillier, a
reproductive
specialist at the University of Pittsburgh in
Pennsylvania, who heads the Microbicide Trials Network sponsored by the
U.S.
National Institutes of Health. Earlier microbicide
studies had all used compounds that attacked HIV nonspecifically, using
surfactants and the like, she notes. “We got a
proof of concept: Topically applied antiretrovirals can interrupt HIV in
women.
Is it good enough? Absolutely not. We want to see
something more effective.” Hillier and others also say they would like
to
see the CAPRISA 004 results confirmed in a second
study.
Hillier is heading just such a trial.
Called Vaginal and Oral Interventions to Control the Epidemic (VOICE),
the study is
comparing two types of pre-exposure prophylaxis:
daily vaginal application of a tenofovir gel and oral administration of
an
anti-HIV drug. (It is testing both tenofovir and a
sister compound, Truvada.) VOICE, begun in September 2009, is expected
to run for 4 years and enroll 5000 women in South
Africa (the Abdool Karims are collaborators) and three other countries
in
southern Africa. “It's going to be important to
have data from more than that very high incidence single site, and it's
important
to see if we can do better with more frequent
dosing of the gel,” says Hillier. Other microbicide researchers are
exploring
what they believe are more potent anti-HIV drugs
than tenofovir and simpler delivery methods like vaginal rings that
periodically
secrete the compounds.
Even if oral pre-exposure prophylaxis
works, many researchers believe a microbicide gel could have many
benefits for women.
For one, only minimal amounts of the drug make it
to the blood system, reducing the risk of side effects. Salim Abdool
Karim
further stresses that prevention strategies, just
like contraception options, are not one size fits all.
The next step for the CAPRISA researchers
is to analyze why some women who received the tenofovir gel still
became infected.
“What undermined tenofovir's ability to protect
some of those women?” asks Salim Abdool Karim. “We need to go back into
the
lab and understand why we didn't see a better
effect to find potential avenues to try and do better.”
Science
23 July 2010: Vol. 329
no. 5990
pp.
374-375
DOI:
10.1126/science.329.5990.374
