Stanford Study Finds HIV Drug Can Persist in Mothers' Milk, Increasing Risk to Them...

Stanford Study Finds HIV Drug Can Persist in Mothers' Milk, Increasing Risk to Them and Their Babies

STANFORD, Calif.--(Business Wire)--
A drug commonly used in the developing world to prevent
transmission of HIV from mother to child persists in the breast milk
and blood of the mothers, putting them and their babies at risk for
developing drug-resistant strains of the virus, according to
researchers at the Stanford University School of Medicine.

The researchers found that the drug, nevirapine, stays in the
blood and breast milk of the infected mothers for at least two weeks.
During that time, the virus has ample opportunity to transform itself
into drug-resistant strains of HIV, the human immunodeficiency virus
that causes AIDS, which can be very difficult to treat.

"In the short term, nevirapine is better than nothing," said David
Katzenstein, MD, professor of infectious diseases and principal
investigator of the study. "But in the long term, I'm concerned about
conferring resistance. If you're talking about resistance on a broad
scale, it could jeopardize future treatment for mothers and infants."

Seble Kassaye, MD, instructor in infectious diseases and first
author of the study, will present the results Aug. 5 at the
International AIDS Conference in Mexico City.

Last year, 420,000 babies were born HIV-positive, the large
majority of them to HIV-infected mothers in sub-Saharan Africa,
according to figures from the United Nations Joint Programme on
HIV/AIDS. The centerpiece of public health programs in the developing
world to stop mother-to-child transmission of HIV are both zidovudine
(AZT) and nevirapine, which have been used as preventive tools in
nearly 900,000 women and infants worldwide. The drugs are relatively
inexpensive and easy to administer, and nevirapine is typically given
as a single pill as the mother goes into labor and as a liquid to the
baby just after birth. Use of the drug reduces the chance of HIV
transmission by half, to about 13 percent. However, not all
HIV-infected women have access to one or both of these drugs,
especially in sub-Saharan Africa.

In addition, nevirapine has proven to be problematic. Previous
studies have found that as many as 69 percent of HIV-positive mothers
and as many as 80 percent of babies born infected, even after being
given a single-dose of nevirapine without AZT, may develop
nevirapine-resistant strains of the virus.

In the latest study, the Stanford scientists set out to better
understand this problem.

They looked at a group of 32 HIV-positive pregnant women in
Zimbabwe, where Katzenstein and his colleagues have had ongoing
research and clinical programs in HIV/AIDS for more than a decade. The
sub-Saharan African country has been hard hit by the virus, with an
estimated 17 to 18 percent of young adults estimated to be infected.
Among pregnant women, some 20 percent are thought to carry the virus.

In recent years, Zimbabwe has begun offering antiretroviral drugs
to a limited number of infected patients, but at the time of the
study, none of the women had been treated for their HIV. The only drug
they received was the single dose of nevirapine when they went into
labor, largely for the sake of their babies.

The researchers found that the drug persisted in the body for
weeks, with more than half of the women having detectable levels in
their blood within two weeks after delivery. Two-thirds had measurable
levels in their breast milk at two weeks, the researchers found.

The longer the drug remains in the system, the more likely it is
to promote development of mutations in the virus. Although none of the
HIV-infected women carried drug-resistant strains of the virus at the
outset of the study, at two months after birth RNA tests showed a
third of them had drug-resistant virus in their blood. Sixty-five
percent had drug-resistant strains in their breast milk as well, with
the potential to pass this on to their babies through breastfeeding, a
common mode of viral transmission.

The mothers who were most likely to develop resistant virus were
those whose disease was more advanced as indicated by lower CD4 cell
counts, the immune cells targeted by HIV, Kassaye said. With advanced
HIV infection, these women are likely have more replicating virus, so
they may be more prone to developing mutations that make the virus
resistant to treatment, she said.

If these women had access to better, combination antiretroviral
treatment to optimally suppress virus replication, they might be less
likely to develop these hard-to-treat strains later, she said.

"It reinforces the need to treat these women with combination
therapy, thereby providing better prevention for the infant, while
providing better treatment for the mother," Kassaye said. "Public
health efforts should continue to expand combination therapy so that
mothers and babies aren't left vulnerable to drug resistance."

Combination therapy is a mix of drugs that is more expensive--and
thus less accessible--in the developing world. In the United States,
HIV-positive women receive a highly effective form of combination
therapy that has reduced transmission of HIV from mother to infants to
less than 2 percent.

Other study authors at Stanford include Yvonne Maldonado, MD,
professor of pediatrics; Elizabeth Johnston, PhD, research associate;
Esther Lee, former graduate student; and Avi Shetty MD, former
postdoctoral fellow in pediatric infectious disease.

The work was fund by a grant from the Doris Duke Charitable
Foundation and by the National Institutes of Health.

Stanford University Medical Center integrates research, medical
education and patient care at its three institutions -- Stanford
University School of Medicine, Stanford Hospital & Clinics and Lucile
Packard Children's Hospital at Stanford. For more information, please
visit the Web site of the medical center's Office of Communication &
Public Affairs at http://mednews.stanford.edu.

Stanford University Medical Center
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