The first decade of the HIV epidemic was a gruesome horror show of human bodies wasting away. Then, miraculously, succeeding waves of new drugs added flesh to withered bodies that arose like Lazarus from the near dead. HIV infection quickly became a treatable, manageable chronic disease.
HIV prevention, on the other hand, has been a far slower, incremental and less successful endeavor. The most recent step of progress is something called a dapivirine ring. The concept is simple: Women use a silicone elastomer vaginal matrix ring that dispenses an anti-HIV drug—similar to ones used to dispense birth control hormones—and are protected from HIV infection for a month.
According to researchers who tested the ring on more than 4,500 African women between the ages of 18 and 45, the concept works. Women who used the ring were 27 percent less likely to become infected with the HIV virus, according to data presented last Monday at the annual Conference on Retroviruses and Opportunistic Infections in Boston.
The Joint United Nations Programme on HIV/AIDS estimates that at the end of 2014, 36.9 million people were infected with HIV worldwide, most of whom live in developing countries. Women are more likely than men to be infected with the virus in sub-Saharan Africa where they constitute 58 percent of all people living with HIV.
Digging deeper into the data yielded some insights: First, adherence was key; the product cannot work if it is taken out rather than worn the entire month. There is evidence that many removed the ring for at least some period of time during the month. Efficacy crept up to 37 percent in women who really did use the ring, as evidenced by the amount of the drug in their blood. Second, age was a huge predictor of adherence and protection—the ring showed more effectiveness in older women. Efficacy was 61 percent in women 25 years of age and older whereas it was only 10 percent in those who were younger. That info could give researchers better insight as to why half of all new HIV infections worldwide occur in younger persons as well as devising methods for changing those numbers.
Despite the lower success rate in younger participants, the good news is that the vaginal ring still showed some success in terms of protection, unlike earlier trials of woman-controlled HIV prevention such as microbicides, says Jared Baeten, who led the study, published in this week’s The New England Journal of Medicine. Now that the ring has proved it can work, he hopes additional trials will uncover ways to make it work better, just as they have done with the pill form of prevention known as preexposure prophylaxis, or PrEP.
First participants in any drug or product clinical trial really are asked to take a leap of faith, Baeten explains. They are told they might get a drug or they might get a placebo, and the drug might work or it might not. “But in later open-label studies we know the drug works and that everyone is getting it,” he adds. That can change adherence. “It opens up a lot more conversation about whether or not this is right to use, when to use, how to use and how much protection it can really provide,” Baeten says. “None of those questions can be answered in a blind clinical trial. Both adherence and efficacy were actually higher in the open-label studies of PrEP. That is something that rarely happens in clinical medicine.”
Naturally, other researchers, such as Sharon Hillier, a University of Pittsburgh researcher who focuses on microbicides and other products to protect against HIV infection and who was not involved with this particular study, wanted the effectiveness to be much higher. “But I believe for the first time you can use tiny amounts of antiretroviral drugs applied topically in a really safe way and get a significant reduction in HIV infection for women, and that for me is pretty cool,” she says.
Like many, Hillier thought that an injectable product or vaginal ring would overcome the adherence issue. “But I think that barriers for the youngest people really transcend route of delivery,” she says. “Teenagers have a much more defiant life perspective and a much greater sense of being invulnerable.”
Experience has taught Hillier it probably is better to enroll older participants in a proof-of-concept study; when subjects are told they may receive a placebo and it is not known if the real product works, they are more likely to be adherent. Once a product is shown to be effective researchers can work on methods to engage younger people.
“We need to figure out what women really want,” says Carl Dieffenbach, director of the Division of AIDS, National Institute of Allergy and Infectious Diseases who oversees more than a billion dollars of National Institutes of Health–funded AIDS research and was not involved with the study. “This is just a step along the way. Do we do better if we offer women protection from pregnancy as well as protection from HIV?” The next studies might have both birth control and antiviral properties or perhaps just contraception instead of a placebo. Pregnancy in both arms of the study would be a way to measure adherence. “That may change the equation” on getting younger women to use it,” Dieffenbach says. He is convening a meeting in March to examine options for the next prevention trials.
“In many settings not getting pregnant so often is a very high priority for women, often even higher than not getting HIV in settings like Africa, Baeten says. “Pregnancy prevention might be the hook to use the ring and HIV prevention may be an additional benefit.” Hillier echoes that feeling. If her own teenage daughter chose to use a contraceptive ring as birth control, she hoped it would also protect against HIV.
There are no silver bullets for HIV prevention, Hillier says. The struggle will be to continue to add options and expand the choices that people have in choosing to protect themselves from the infection.