Analysis by Jim Pickett
Research into new HIV prevention technologies scored a huge victory July 20 at the XVIII International AIDS Conference ( AIDS 2010 ) in Vienna, Austria. There was nary a dry eye in the house.
At 1 p.m. that day, the husband and wife team of Drs. Salim S. Abdool Karim and Quarraisha Abdool Karim, from the Centre for the AIDS Programme of Research in South Africa ( CAPRISA ) , announced that a vaginal gel had been shown to significantly reduce a woman's risk of being infected with HIV and genital herpes too. ( Microbicides are substances currently in development that are designed to reduce or prevent the sexual transmission of HIV or other sexually transmitted infections when applied either in the vagina or the rectum. )
The microbicide gel the Karims studied contained 1 percent tenofoviran antiretroviral drug commonly used to treat people living with HIVand was found to be 39 percent effective in reducing a woman's risk of becoming infected with HIV during vaginal intercourse and a whopping 51 percent effective in preventing genital herpes infections among the women in the trial. The protective effects against HIV increased as the use of tenofovir increased, so that women who used the gel in more than 80 percent of their sex acts during the trial had a 54 percent reduction in HIV infections.
If and when other studies of tenofovir gel confirm these results, widespread use of the gel, at this level of protection, could prevent millions of new HIV infections among women over the next two decades. This is especially important for South Africa, where the global pandemic is the most severe. In rural Vulindlela, outside Durban, one of the trial's two sites, the prevalence of HIV among young women exceeds 50 percent by the time they reach the age of 24. A microbicide gel would put the power of prevention in these women's hands, especially important where monogamy is not a guarantee and condom negotiation is difficult.
At the conclusion of the Karim's presentation, an overflow of more than 5,000 researchers and advocates stood up and gave them a prolonged standing ovation. Hugs, tears, and high fives heightened the excitement and electricity in the airnone of which normally ( ever? ) punctuate a summary of scientific data.
It was impossible not to feel deeply movedthe audience was witnessing first-hand a historic turning point in the epidemic. We will always remember "before CAPRISA" and "after CAPRISA." The situation before was looking a little grim; many years of research had not yet delivered a product that showed any signs of efficacy. After CAPRISA, it's not exactly rainbows and lollipops, as there is much to be done to confirm and extend these findings and make this drug available… once everyone has dabbed their eyes. But it's quite lovely nonetheless.
As an important aside, tenofovir is also being studied as a form of oral pre-exposure prophylaxis, in which HIV-negative individuals take the drug to prevent HIV transmission. Initial data from a safety and behavioral study conducted by the U.S. Centers for Disease Control and Prevention among 400 men in the United States were reported at AIDS 2010 as well.
"We didn't find any increased risk of harm in medical terms, and on the behavioral side the preliminary work we've done also suggests there is no increased risk," the CDC's Lisa Grohskopf, who led the study and presented the findings, told Reuters.
Later this year or in early 2011, data from the iPrEx Phase III trial will be released. The study will report on approximately 3,000 gay men and other men who have sex with men ( MSM ) from the United States, Peru, Ecuador, Brazil, Thailand and South Africa who are taking the antiretroviral Truvada ( a combination of tenofovir and emtricitabine ) , or a placebo, every day to see if the drug works to prevent HIV infection.
Back to CAPRISA: What do these new findings mean for rectal microbicides? After all, products that can be applied rectally to prevent HIV are important to the millions of gay men and women who practice receptive anal intercourse and need options beyond condoms as well.
"The positive results from the CAPRISA study represent a very significant milestone in HIV prevention research and they increase optimism that we can develop safe and effective antiretroviral rectal microbicides," said University of Pittsburgh's Dr. Ian McGowan, International Rectal Microbicide Advocates ( IRMA ) Scientific vice-chair and co-principal investigator of the Microbicide Trials Network. "Phase I rectal safety studies with tenofovir are ongoing and these efforts need to be intensified to help us move forward to rectal microbicide effectiveness studies as quickly as possible," he said.
Anal intercourse is a common human sexual behavior, practiced by approximately 5-10 percent of the world's general population, including heterosexual women and men, gay men, and other MSM. Because an act of unprotected anal intercourse is 10 to 20 times more likely to result in HIV transmission compared to unprotected vaginal intercourse, it is likely that unprotected anal intercourse is a significant driver in the HIV epidemic overall.
We know that unprotected anal intercourse is the chief cause of HIV infection for gay men/MSM across the world. But the world has largely ignored gay men, and anal intercourse. Gay men are underrepresented in most national AIDS strategies, in epidemiology, surveillance, and in researchif they show up at all. They have been woefully underserved by prevention, care, treatment and support services. Similarly, there is a paucity of data regarding anal intercoursehomosexual and heterosexualdue to politics, stigma, criminalization, and outright denial.
Globally, gay men/MSM are 19 times more likely to be HIV infected compared to the general population. These disproportionate rates extend to Africa, where the epidemic is often characterized as "heterosexual." For instance, according to data from Dr. Chris Beyrer presented at the Global Forum on MSM and HIV's "Be Heard!" pre-conference July 17, HIV prevalence among gay men/MSM in Malawi is 21.4 percent compared to 11.5 percent in the general population; in Kenya, 15.2 percent of gay/MSM are HIV+ compared to 6.1 percent of the general population. Previously reported data from Beyrer revealed that in Uganda, HIV prevalence rates among gay men and other MSM are just above 40 percent compared to 5 percent for other Ugandan men of reproductive age. And in South Africa, the prevalence rates between gay men/MSM and men of reproductive age are almost the sameboth hovering around 15 percent.
Data released by the U.S. Centers for Disease Control and Prevention in early 2010 revealed that gay men/MSM in the United States are 44 times more likely to be HIV-positive than other men, and 40 times more likely to be HIV-positive than women.
The bottom line is that for the men and women who engage in anal intercourse, condoms work quite well to prevent HIV, but many people do not use them, or are simply unable to use them due to a number of issues including power dynamics in sexual relationships, stigma, and a serious lack of availability. According to the Global HIV Prevention Working Group, only 9 percent of individuals at risk for HIV infection had access to condoms in 2008. Condom-compatible lubricants are also in dangerously short supply, especially in Africa. Options are needed.
While the rectal microbicide field has gained significant momentum, more focus and resources are necessary. In 2010, U.S. $7.2 million are being spent globally on rectal microbicide research. IRMA has calculated that annual investments must increase by 40 percent from 2011-2014, to U.S. $10 million/year and must increase further to U.S. $44 million ( a six-fold increase ) in the years 2015-2020 to ensure a minimum of candidate products are moving through the research pipeline into late stage testing for effectiveness.
Advocates are optimistic that the CAPRISA results will not only accelerate the development of safe and effective vaginal microbicides, but that this proof of concept will also be translated into more financial and creative energy into rectal microbicide development. With five new infections for every two individuals beginning treatment, it's absolutely imperative we find new ways to prevent HIV for individuals at risk, gay and straight, women and men.
CAPRISA enrolled 889 women into a double-blind, placebo-controlled, randomized clinical trial. They were instructed to use the gel up to 12 hours before sex and soon after having sex for a maximum of two doses in 24 hours. Participants used the gel for a minimum of one year and a maximum of two and a half years. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. They were asked to return all used and unused gel applicators. A total of 181,000 applicators were dispensed during the study.
In a word, these women were asked to do a lot. And 843 of them did all of that to the very end, with the study achieving a truly extraordinary 95-percent retention rate. The standing ovation, the hugs, and the tears were as much for the scientists as for these incredibly dedicated women and their exceptional, unwavering commitment to making a difference in the epidemic.
IRMA is a global network of advocates, scientists, policy makers and funders from six continents working together to advance a robust rectal microbicide research and development agenda. IRMA is based in the United States at the AIDS Foundation of Chicago with chapters in Latin America and Nigeria. For further information on IRMA visit www.rectalmicrobicides.org and read IRMA's new report, From Promise to Product: Advancing Rectal Microbicide Research and Advocacy. The report provides an overview of the maturing rectal microbicide field, updates the resource tracking exercise IRMA last conducted in 2006, and lays out global advocacy goals and objectives. Importantly, it also calls for the creation of a Global Rectal Microbicide Development plan, which would provide the foundation necessary to move the field from pre-clinical studies through Phase III efficacy trialsfrom promise to product.