This photo provided by the International Partnership for Microbicides shows a ring that is coated with an anti-AIDS drug designed for women to insert into the vagina once a month to reduce the risk of HIV infection. Researchers say women who inserted a vaginal ring coated with an anti-AIDS drug once a month were partially protected against HIV infection. Two large studies in Africa found the effect was modest, reducing overall HIV infection by about a third. But surprisingly, the ring worked far better in women 25 and older, leaving researchers wondering if younger women who got little to no benefit simply didn’t use the device properly. Photo Courtesy: International Partnership for Microbicides via AP

The ring proved safe although the protection was modest, reducing overall HIV infection by less than a third. Surprisingly, the ring worked far better in women 25 and older, leaving researchers wondering if the youngest women, who got little to no benefit, simply didn't use the device properly.

Women make up more than half of the nearly 37 million people worldwide living with HIV, most of them in hard-hit Africa, and scientists have long sought tools to help them protect themselves when their partners won't use a condom.

Despite questions the studies raise, the nonprofit International Partnership for Microbicides said it considered the results promising enough to seek appropriate regulatory approval for wider use in parts of Africa.

"You can't just say, 'Until something is perfect, we're going to wait,'" said Dr. Zeda Rosenberg, founding chief executive officer of IPM. "We have to give women options."

"For a woman to have a prevention tool that she can control is an incredibly important goal," added Dr. Jared Baeten of the University of Washington, who led a National Institutes of Health-funded study of the ring. "I want rings, pills and other strategies to be on the shelf for women so they can make choices for what's going to work for them."

Aside from condoms, HIV prevention tools include taking a daily anti-AIDS pill. That so-called "pre-exposure prophylaxis" isn't widely available in poor countries, and other attempts at HIV-blocking vaginal gels haven't yet panned out.

But the age disparity found in the vaginal ring studies is so puzzling that the NIH plans to consult with outside experts on next research steps.

While women need a discreet form of HIV prevention, "it's going to be absolutely critical" to determine if the younger women really didn't follow instructions, or if there was some biological difference, cautioned Dr. Anthony Fauci, director of NIH's National Institute for Allergy and Infectious Diseases.

Vaginal rings are sold in the U.S. for birth control, but the anti-AIDS version tested in Africa contained no contraception. Instead, it slowly oozes an experimental virus-blocking drug named dapivirine into the surrounding vaginal tissue. Women would replace the ring once a month, when it was time for another dose.

Two studies involving more than 4,500 women in Africa are being presented at the Retrovirus Conference in Boston, comparing women who used the dapivirine ring with those given an identical-looking but drug-free version. It offered modest protection, reducing by 27 percent to 31 percent the participants' overall risk of HIV.

But closer inspection of the large NIH-funded ASPIRE study in Malawi, South Africa, Uganda and Zimbabwe turned up something odd. Ring users who were 25 and older were 61 percent less likely to be infected while those ages 18 to 21 essentially got no benefit, Baeten said.

While the ring is designed to stay in place for an entire month before being replaced, there are signs the younger women didn't use it as regularly, said Baeten, whose results also were published online Monday in the New England Journal of Medicine. He said women had to get comfortable with the how to use a device they'd never seen before, but those who used the ring continuously saw protection that continued throughout the 2½-year study.

"The ring must be used consistently to achieve protection," the IPM's Annalene Nel told reporters Monday as she discussed the second study, called the Ring Study. Conducted in South Africa and Uganda, that study likewise showed a trend toward greater protection for women over 21, she said.

While that study isn't completed yet, the IPM said South African regulators asked researchers to switch all the remaining study participants to the dapivirine-coated ring rather than the placebo version.

Early studies of those daily anti-AIDS pills also found less protection in younger people, who did better at sticking with the tablets only after their effectiveness was proven, said Mitchell Warren, executive director of AVAC, which advocates for a range of HIV prevention tools. He said there is "a global imperative" to answer remaining questions about the ring.