A vaginal microbicide can cut HIV infection rates by 39 percent in women, researchers announced Monday. And female study participants who inserted the gel as directed reduced their chances of contracting HIV by more than half (54 percent). The news is a stunning, positive development— especially for women at risk for sexual transmission—in a field that has been plagued by two decades of failed and aborted trials.
A reliable HIV-prevention method for women has thus far proved hard to come by, leaving many millions of at-risk women subject to their partner's decision about condoms.
But a gel that can be applied discretely could severely cut back on HIV, a disease that currently infects an estimated 33 million people worldwide. Researchers involved in the new study calculated that if about a third of women in South Africa could use this gel, in the next 20 years, 1.3 million HIV infections—and 820,000 HIV-related deaths—could be prevented in that country alone.
The gel was made with 1 percent of the antiretroviral medication tenofovir (a drug also sold in tablet form as Viread or in the combination treatment Truvada), which stops HIV from replicating inside a person's cells. It is the first of half a dozen candidates to show robust prevention. It was tested, starting in 2007, in a double-blind, randomized controlled trial of 889 sexually active women ages 18 to 40, in the KwaZulu-Natal province, which is "at the epicenter of South Africa's 'explosive' HIV epidemic," wrote the study's researchers, led by wife and husband team Quarraisha Abdool Karim and Salim Abdool Karim, of Center for the AIDS Program of Research in South Africa (CAPRISA) and the Department of Epidemiology at Columbia University's Mailman School of Public Health in New York, respectively.
"Current HIV prevention behavioral messages on abstinence, faithfulness and condom promotion have had limited impact on HIV incidence rates in women, especially in sub-Saharan Africa," the researchers wrote. "This antiretroviral microbicide could potentially fill an important HIV prevention gap, especially for women unable to successful negotiate mutual monogamy or condom use." The gel was recommended to be used up to 12 hours before an anticipated sexual encounter and again up to 12 hours afterward (but with no more than two doses in one 24-hour period). The results of the trial are slated to be presented July 20 at the International AIDS conference in Vienna and were published early online July 19 in Science.
"This is a historic day for HIV prevention research," Mitchell Warren, AIDS Vaccine Advocacy Coalition executive director, said in a prepared statement. The findings are "the first clinical evidence that a microbicide gel can help to prevent the sexual transmission of HIV infection" and are "a great boost to the microbicide field," he noted.
But this use of tenofovir has yet to be approved by any regulatory bodies and thus, it cannot be sold or marketed. And Salim Abdool Karim explained, in a July 19 teleconference, that the work is only "a proof of concept study" and that further research need to be completed to see if the finding can be replicated—and perhaps why more women who used the active gel were not protected. He estimates that it will be at least a year or two before any similar product will be available on the market.
Previous tests of microbicides have failed to generate substantial protection, and in one trial even raised the rate of transmission. "It's very easy to get depressed," Polly Harrison, founder of the Alliance for Microbicide Development, told ScientificAmerican.com in 2008 in discussing previous gel trial failures.
The researchers attribute part of the gel's success to the fact that it works differently than some previously tested vaginal microbicides that depended on a full vaginal surface covering to protect against transmission. "Tenofovir is not surface-active," Salim Abdool Karim explained at the press briefing. "It goes into the target cells, so it acts at a different point" in the infection process.
As an antiretroviral, tenofovir also cuts the rate of herpes simplex virus 2 transmission, a virus that effectively doubles a woman's chances of getting HIV, Salim Abdool Karim noted. Although the study was not designed to study this aspect of tenofovir, "it would reduce the presence of HSV-2 in the long term," thereby likely also helping to reduce HIV rates, he said.
Although the transmission rate was much improved over previous vaginal microbicide gel studies, 39 percent is hardly a perfect solution—it is not wildly higher than the researchers' pre-study goal of a 33 percent efficacy cut off. Nevertheless, the success rate might pack some surprises for the microbicide community. "I think most people here are skeptical that it's going to work," Salim Abdool Karim said from the International AIDS conference in Vienna.
The gel's effectiveness also seemed to taper off over the 30-month study period. 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.
If the gel does get approval from South African regulatory bodies, it might make it into clinics cheaply, as the Contraceptive Research and Development program and tenofovir maker Gilead Sciences agreed that the South African government could make the product without paying royalties. The new results join other encouraging preventive findings, including the November 2009 news that an HIV vaccine trial in Thailand had met with a 26 to 31 percent effectiveness rate. Other trials testing different dosing of tenofoir and other antiretroviral microbicide gels for HIV prevention in women are ongoing.
Image courtesy of iStockphoto/Eraxion