Endeavors magazine: Blocking HIV in the Womb

Blocking HIV in the Womb

Can a mutant gene save children from AIDS?

by Prashant Nair

[filed under: public health; article date: january 2008]

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More than half a million children worldwide are infected with HIV every year. Most live in sub-Saharan Africa and get the virus from their mothers while still in the uterus, during delivery, or through breastfeeding.

But less than a third of infected mothers pass on the virus to their babies. Steven Meshnick and his team of researchers at Carolina’s School of Public Health uncovered a genetic mutation that might protect babies from picking up the virus from their mothers before or during birth.

The team studied a group of 552 HIV-positive Malawian women and their infants and found that differences in the gene for a human protein that binds HIV accounted for the difference in mother-to-child transmission of HIV. The protein CCR5 sits on the surface of immune cells and latches onto chemical messengers that help the body fight infection. HIV subverts CCR5, among other proteins, by latching onto it and gaining entry into human cells.

Meshnick’s team found differences in the CCR5 gene in babies that were infected and in those that were not. A single nucleotide-base change in CCR5 made the uninfected babies’ white blood cells resistant to infection by HIV. The mutation probably decreased the amount of CCR5 on the surface of the white blood cells. But these babies were only protected if the amount of virus in the mother was below a certain threshold. Above it, the babies were infected regardless of the CCR5 mutation.

“Mother-to-child transmission is a big problem in Africa, but not here,” Meshnick says. During the middle of pregnancy, infected mothers in the United States get antiretroviral drugs that prevent further infection and curb disease progression. They also get cesarean sections, which greatly reduce the chances of infection for the baby, Meshnick says. But fewer than 10 percent of eligible women have access to antiretroviral drugs in sub-Saharan Africa.

The findings suggest that drugs that block or reduce the amount of CCR5 on white blood cells without harming the mother could protect against HIV in high-risk populations. But the study is only meant to serve as a jumping-off point for a more exhaustive analysis of other genes that could be involved. “We’ve only scratched the surface with CCR5,” Meshnick says. “We’re now planning a genome-wide hunt for genes that may be protective.”

Understanding the genetic basis of mother-to-child transmission is crucial to uncovering exactly how HIV gets transmitted, he says. “This could help us develop drugs and possibly a vaccine to prevent AIDS.”

Joseph Eron, a scientist at Carolina’s Center for Infectious Diseases, says the study clearly demonstrates that the human genetic makeup influences the likelihood of passing on HIV from mother to child. “These results raise the possibility that newly developed HIV medications that inhibit HIV replication by blocking the CCR5 receptor might be useful in interrupting mother-to-child transmission of HIV,” Eron says.

In August 2007, the FDA approved Maraviroc, the first CCR5 inhibitor drug that can be taken orally. Though Maraviroc didn’t cause serious side effects in clinical trials, the drug hasn’t been studied long enough to rule out less common side effects.

Prashant Nair is a master’s student in medical journalism at Carolina.

Steven Meshnick is a professor of epidemiology in the School of Public Health. His study appeared in the September 5, 2007 issue of the journal PLoS One. The study’s lead author was Bonnie Pedersen, also of the School of Public Health. The study was funded by the National Institutes of Health and Carolina’s Center for AIDS Research.