Microbicide might protect pregnant women from HIV
Susceptibility is high for them
The world has well-embraced antiretroviral treatment (ART) for the prevention of HIV transmission between women and their newborn babies through transmission during pregnancy or nursing. And these strategies have proven to be a huge success.
But there's another risk involving pregnant and lactating women, and that involves the possibility that an uninfected woman will become infected with HIV while she is pregnant or nursing an infant.
"We know that one of the worst times to get HIV for women is when they're pregnant or lactating," says Richard Beigi, MD, MSc, an assistant professor of reproductive sciences at the University of Pittsburgh (PA).
"There are data suggesting that pregnant women are more susceptible to getting HIV if they come in contact with it," Beigi says. "They're also more likely to transmit it to their male partner."
More importantly, if a woman gets HIV while pregnant then the risk is greatly increased that the virus will be transmitted to her baby. And the same is true for women who contract HIV while breastfeeding, he adds.
The problem is determining a prevention strategy that poses no risk to the pregnant woman and her fetus or newborn.
Research into the safety of prevention or treatment strategies involving pregnant women are almost never done.
"What happens is pregnant and breastfeeding women are almost always excluded from these trials," Beigi says. "The drug goes to the market and then people might do studies, but there are very little data on the drug in pregnant women prior to it going on the market."
Now researchers believe they have found a solution to this dilemma. For the first time ever, there is a microbicide that is being tested as an HIV prevention gel in pregnant and lactating women. The Microbicide Trials Network, funded by the National Institutes of Health (NIH), is studying the use of a vaginal microbicide tenofovir gel in breastfeeding women and pregnant women. The trial is called MTN-008 and it's a follow-up to MTN-002, which found that a pregnant woman given a single dose of tenofovir gel before a scheduled Cesarean delivery was safe and well-tolerated by both the mother and infant. The infant's umbilical cord blood showed drug levels that were 40 times lower than drug levels in studies of HIV-infected women who took the tablet form of tenofovir while they were pregnant.
"This is a drug we know about and it has a clean record of safety with minimal exposure to the mom and with minimal blood absorption ," Beigi says. "Because of the potential direct benefit to the women, the IRB gave us clearance."
The Phase I trial is underway at the Magee-Womens Hospital of the University of Pittsburgh Medical Center and the University of Alabama, Birmingham.
"This study is a follow-up to our first study of 16 women at term pregnancy," Beigi says. "For this one, we're enrolling 90 pregnant women in sequential manner and giving them one week of dosing."
Results from the earlier study were very positive, finding that the microbicide could protect against both HIV and herpes infection, he adds.
"New herpes infection in any pregnancy is a very serious problem," he explains. "They are many more times likely to pass that on to their child, and it's an absolutely devastating condition in babies."
Goal: Early administration
The study's goal is administer the microbicide earlier in the pregnancy to determine safety.
Tenofovir gel possibly could become the first vaginal microbicide approved for preventing HIV infection in women. In an earlier clinical trial of tenofovir gel, called CAPRISA 004, investigators found 39% fewer infections among HIV-negative women who used it before and after vaginal sex compared with women who used a placebo gel. The Vaginal and Oral Interventions to Control the Epidemic (VOICE) study is enrolling 5,000 women in southern Africa to see if daily use of the gel or an antiretroviral tablet can reduce HIV infection risk. The results of VOICE are expected to be announced in 2013, and its approval by the Food and Drug Administration (FDA) for marketing could follow those results.
Tenofovir is a good pick for a microbicide because it has been well-studied and long used, Beigi notes.
"It's already given in oral form to control the virus levels in people who have HIV, and that product has been formulated into a gel for pre-exposure prophylaxis to prevent new infections," he explains. "It's been very beneficial to us that we already had a safety record established among pregnant women who used the drug, so we feel comfortable using the gel with pregnant women."
Researchers have learned that tenofovir is minimally absorbed in the bloodstream. Early investigation suggests the tenofovir gel results in 40% less HIV infection among non-pregnant women randomized to its use when compared with those on a placebo, Beigi says.
"We're now studying this drug carefully in pregnant women so if efficacy is established then they can use the drug too," he adds. "We investigated the impact on the fetus in our first study, and it looks like the drug does cross to the fetus, but it looks like it is barely detectable, and we don't believe there's any risk of impact on the fetus."
If this investigation proves successful, the next planned investigation would be a multinational study with a longer dosing period and many more women enrolled, he says.
The current trial will enroll 105 women, including 15 who are breast feeding and 90 who are pregnant. The pregnant women are enrolled late in their pregnancy and given the gel for seven straight days. They are monitored as they go into labor, and the babies are followed for a year post-delivery. There should be some results available by the fall of 2012.
"We're focusing on women who are HIV negative and will be eventual users of the product," Beigi says. "If it's shown to be beneficial, it could be used in any part of the world, and the biggest impact would be in areas where there's a higher prevalence of HIV."