Blocking HIV at the Root.
by Margarite Nathe
In Malawi, a narrow ribbon of a country in southeastern Africa where more than 14 percent of the population is infected with HIV, Steve Meshnick and his team of researchers collected data and samples from 149 HIV-positive pregnant women. When they got home to their labs, they took what may be a step forward in HIV prevention and our understanding of how the virus is spread.
“Mother-to-child transmission — or vertical transmission — is a huge problem,” Meshnick says. Over half a million babies are infected at birth every year. When infected mothers don’t take antiretroviral drugs during delivery, their babies contract HIV about 25 to 35 percent of the time.
The women who participated in Meshnick’s study received a single dose of an antiretroviral drug when they went into labor. Doctors in the United States usually give HIV-positive mothers three doses to help prevent transmission, but the antiretroviral drugs are too expensive for hospitals in Malawi to keep in stock. While most of the mothers in the study did not transmit the virus to their babies, some did. And the researchers think they may have figured out why.
Usually, the mother’s blood never mixes with the blood of the fetus. The placenta, a paper-thin layer of cells, separates the blood of the two individual beings. The connection between mother and child comes in the form of villi, which Meshnick describes as “the baby’s roots in the maternal soil,” stretching into the placenta to absorb filtered oxygen and nutrients. “There’s never any real mixing, and there shouldn’t be. So the question becomes, is there some sort of mixing that occurs abnormally, and is this mixing possibly responsible for some of the transmissions?”
The villi (red and blue) act as “fetal roots in the maternal soil” by filtering nutrients and oxygen through the placenta. Image: UNC Medical Illustration.
The researchers found that placental alkaline phosphatase (PLAP), an enzyme which normally exists in the placenta, was present in the umbilical cord serum of some of the babies. PLAP is too large to get through the placental barrier to the fetal bloodstream and, the researchers concluded, must have gone through a small fissure in the placenta. It turned out that in the cases where PLAP was present in the cord serum, the babies were almost always infected.
During delivery, microtransfusions of virus-laden blood escaped from tears formed in the placenta during the mothers’ contractions. The maternal blood leaked to the umbilical cord and into the baby’s circulation. Although they had rested in the womb safely for nine months, the babies were infected during their perilous last moments there.
“There are three ways to stop vertical HIV transmission,” says Jesse Kwiek, a postdoctoral fellow on Meshnick’s team and lead author of the research report. “Chemotherapy and antiretroviral drugs, elective cesarean sections, and not breast-feeding.” While all of these things are easily attainable here in the United States, where there were fewer than a hundred cases of vertical transmission last year, they’re far out of reach in Malawi and many other African countries. Medical treatment and drugs are expensive and often unavailable. Hospitals lack the staff and resources to perform elective c-sections regularly. And even when they can find and afford formula for their babies, women who do not breast-feed their children are stigmatized and suspected of carrying HIV.
HIV infections are always comprised of multiple genetically distinct viruses, which mutate often and rapidly. The next step in the team’s research, Kwiek says, will be to determine the virologic mechanism of HIV transmission, actually characterizing the virus the mother is carrying as opposed to the virus transmitted to the infant. “We want to find out whether it’s a randomly selected virus transmitted from the mother to the infant, or if there’s some sort of viral determinant that makes certain ones more likely to be transmitted,” he says.
“For me,” Kwiek says, “the most frustrating part is that we know how to stop vertical transmission. But for economic and infrastructure reasons, they can’t implement what we already know in Malawi.”
Although these results bring us a new understanding of the way HIV spreads, the public health implications aren’t immediately obvious. “No one has really looked at this before, and we’re just sort of starting,” Meshnick says. “It’s a nice beginning.”
Steve Meshnick is professor of epidemiology at Carolina’s School of Public Health. Jesse Kwiek is a postdoctoral scholar at Carolina and lead author of the report “Maternal-Fetal Microtransfusions and HIV-1 Mother-to-Child Transmission in Malawi.” Other researchers involved in the project include graduate student Alisa Alker, professor of medicine William Miller, and University of Malawi researchers Victor Mwapasa, Eyob Tadesse, and Malcolm Molyneux.
Margarite Nathe is a writer and editorial assistant at Endeavors magazine.
