IAC: Vaginal Ring Promising As Microbicide Carrier

TORONTO, Aug. 17 -- An intravaginal ring, similar to those used to deliver contraceptives and hormonal agents, is a promising way to deliver anti-HIV microbicides, investigators reported here.

In a preliminary placebo-controlled double-blind study, a silicone elastomer ring, with a core containing an investigational HIV medication, released the drug at therapeutic levels and a constant rate in the vaginal tract for several days, they said at the 16^th International AIDS Conference.

While most research on microbicides has focused on topical gels, a ring-based medication would "potentially reduce the compliance burden" on the women who use it, since it would not have to be applied at or near the moment of sexual intercourse, said Joe Romano, Ph.D., of the International Partnership for Microbicides of Silver Spring, Md., and colleagues.

The value of microbicides in the fight against HIV/AIDS was a running theme at the conference, with Microsoft billionaire Bill Gates, among others, suggesting they might be a key weapon that could turn the tide.

The medication tested in the rings is TMC120, or daviripine, a non-nucleoside reverse transcriptase inhibitor that is being developed by the Belgian pharmaceutical company Tibotec, Dr. Romano said. The company and his jointly supported the study.

"It's the concept that we are trying to see whether it's acceptable (to women) and safe," said Jens Van Roey, M.D., of the Belgian company. A next step -- and one that would likely require a large clinical trial - would be to see whether the product actually protects women against HIV infection.

"We can't say it works," Dr. Van Roey said. "That will have to wait for Phase III trials."

But in the small study reported here, Dr. Romano said, the ring, tested for seven days, consistently released medication at 90 times the so-called EC₅₀ - the concentration that produces 50% of the maximum desired effect in vivo.

However, the medication was found at high levels in vaginal fluids and tissues near the ring - the introitus, vaginal wall, and endocervix - but not in the plasma, where it was barely detectable at a level of just over five picograms per milliliter, he said.

In the study, 13 women had a vaginal ring with TMC120 and three had a placebo ring. The safety profile was good, Dr. Romano said:

• There were no consistent and clinically relevant changes in laboratory parameters.
• There were no clinically relevant changes in urinalysis or vital signs.
• There were no major changes in vaginal ecology pH.

One women had a cervical uterine ulcer discovered on day 14 of the study (a week after the rings were removed) but Dr. Romano said the investigators do not think it is drug-related.

There were also six cases of Grade 1 vaginal bleeding after removing the rings, four in the treatment group and two in the placebo arm. The events might have been related to oral contraceptive use, Dr. Romano said.

The rings were safe and well-tolerated, he concluded.

While most research so far has focused on microbicide gels or creams, "there will not be one tool that all men and women will like," commented Lut Van Damme, M.D., Ph.D., of the Contraceptive and Research and Development Program, based at the Eastern Virginia Medical School in Arlington.

But she cautioned that so far no microbicides have been shown to work to block HIV infection. "Once the proof of concept has been established, then it will be necessary to fine-tune," she said.

When that time comes, she added, the vaginal ring will be "a very interesting approach" because it would allow women to be defended at all times against HIV infection, in stead of needing to be applied just before sex.