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Could an anti-HIV vaginal ring be on its way?

Population Council Vag Ring.JPG

Julie Sitney/Population Council

Vaginal rings – such as the NuvaRing – have offered alternative contraceptive options for women looking to delay pregnancy or regulate their hormonal cycle.  Now, a new type of vaginal ring could also help women prevent contracting sexually transmitted diseases.

Researchers from the Population Council, an international non-profit research organization based in New York City, have developed an ‘anti-HIV’ ring, which has successfully blocked HIV transmission in macaque monkeys.  The ring works essentially like other vaginal rings, by constantly delivering a microbicide called MIV-150 inside the vagina.

An allosteric enzyme inhibitor, MIV-150 does not bind to the active site of HIV growth.  Instead the microbicide binds to an enzyme away from the active site, which stops HIV from spreading.

“It essentially blocks HIV replication,” Tom Zydowsky, senior scientist at the Population Council’s Center for Biomedical Research and lead scientist of the study, told FoxNews.com.  “It doesn’t change the shape of HIV, but it changes the shape of a key enzyme that HIV uses to reproduce.  There are all of these steps in the HIV life cycle – one of them we’re blocking with MIV-150.”

Tested in the early 2000s, MIV-150 was found to be ineffective as an oral agent, because the drug was poorly absorbed into the bloodstream.  The agent was also very actively cleared in mammals, so it’s low bioavailability and low half-life did not make it an attractive option for treatment.

However, by having MIV-150 constantly delivered in the localized area of the vagina, Zydowsky and his colleagues were able to overcome the obstacles the drug posed as an oral agent.

“The MIV-150 gets released into the vagina, and it works by getting absorbed into tissues where the infection starts,” Zydowsky said.  “It then …  latches on to some of the virus before it attacks the cells.  It doesn’t have to be in the blood stream, it has to be more localized in the vagina.”

The scientists created the anti-HIV rings with ethylene vinyl acetate (EVA), and inserted them in the macaques either two weeks or 24 hours before the monkeys were exposed to SHIV – a combination of both HIV and the monkey version of the virus, SIV.  The rings were removed either just before virus exposure or two weeks after virus exposure.

Regardless of the time of insertion, the MIV-150 rings significantly blocked HIV transmission in the macaques.  Only two out of 17 test subjects with the ring became infected, while 11 out of 16 subjects, who were given placebo rings, contracted the virus.  Overall the rings provided an 83 percent protection from HIV.

However, the rings did not provide protection if they were removed immediately before virus exposure.  Four of seven monkeys became infected, meaning the rings provided only 16 percent protection from HIV in that scenario.  According to the researchers, this means that women would need to use the rings at all times in order for them to be most effective.

Now that their tests have shown the anti-HIV rings to block HIV transmission, Zydowsky and others at the Population Council are hoping to develop rings with MIV-150 for future commercial use.  However, the ring will have more than just the microbicide inside.

“We’re not developing an MIV-150-only ring for a couple of reasons,” Zydowsky said.  “We’re concerned about resistance development during mono-therapy.  Inevitably, viruses are good at mutating and coming up with resistant strains.  We’re going in with this combination of MIV-150 and zinc acetate – shown it’s much more effective than MIV-150 alone.”

Not only do they hope to boost the rings efficacy, the researchers also have grander plans for their ring – hoping to develop one that will protect women from more than just HIV.

“By adding zinc acetate, we have the potential to pick up herpes, which is a worldwide problem,” Zydowsky said.  “So maybe we also throw in something to tackle HPV – a huge medical need throughout the world.  One scenario would be to get maximum bang for the buck; if we can get a ring to tackle multiple STIs, that would be a great thing.”

Going even further than that dream, Zydowsky said the ultimately goal would be to develop a ring with dual protection – providing both HIV prevention and contraception.  Since the Population Council has a patent on MIV-150, they’re hoping to move forward as quickly as possible to have a ring for humans in the near future.

“We’re projecting five to seven years, because we have additional preclinical testing to do,” Zydowsky said.  “We’re being both realistic and optimistic.  We think we have some good choices and good timelines.”