HIV drugs in breast milk may help protect infants

OB/GYN News, Nov 15, 2004 by Diana Mahoney

BOSTON -- High levels of antiretroviral drugs measured in the breast milk of HIV-positive mothers and in the blood of their breast-fed infants could protect against transmission of the virus from mother to baby, Roger L. Shapiro, M.D., said at the annual meeting of the Infectious Diseases Society of America.

His study's "surprising" findings also suggest that it may not be necessary to prophylactically treat infants of infected mothers directly, provided the at-risk babies are getting therapeutic doses of the highly active antiretroviral drugs from their mothers' milk, reported Dr. Shapiro of the Harvard School of Public Health in Boston.

It is standard practice for physicians to advise HIV-positive women to take antiretroviral drugs while pregnant and during childbirth to prevent transmission of the virus to their babies. The babies themselves are also routinely treated with daily doses of an antiretroviral drug such as zidovudine (AZT) for up to a month, sometimes in combination with a single dose of nevirapine at birth, Dr. Shapiro said.

Breast-feeding is typically not recommended for infected mothers, however, because as many as one in eight babies born to women with HIV/AIDS acquires the virus during breast-feeding, he said.

Because formula feeding is not a reasonable option for some women, particularly those in developing countries with limited access to infant formula and clean water, researchers worldwide have been investigating options for preventing transmission of HIV during breast-feeding. Toward this end. Dr. Shapiro and his colleagues at Harvard sought to determine what, if any, therapeutic or protective effect maternal antiretroviral therapy could have on breast-fed infants.

The investigation, which was part of a larger transmission-prevention study funded by the National Institutes of Health, included 20 HIV-positive breast-feeding mothers with full-blown AIDS in Botswana. All of the women had been placed on an antiretroviral combination drug regimen comprising nevirapine (NVP), lamivudine (3TC), and zidovudine (AZT). Their infants also received a single dose of nevirapine and oral AZT during the course of breast-feeding.

Laboratory testing at 2 and 5 months after birth showed high levels of all three drugs in the mothers' breast milk samples. Blood tests showed that the infants might have achieved high enough levels of NVP and possibly 3TC and AZT from breast-feeding to prevent transmission of the virus through breast milk, said Dr. Shapiro. "What was surprising about what we found is that the infants of mothers who were receiving [the drug combination] had higher than expected levels" of NVP and 3TC, he said.

At 971 ng/mL, the median serum concentration of NVP was 36-360 times higher than the IC50 (the level that inhibits 50% viral growth in vitro) for that drug. The 3TC levels ranged from 0.8-47 times the IC50 levels, which "was higher than we expected it to be, but still lower than what we want the target concentrations for prophylaxis to be," said Dr. Shapiro. The serum levels of AZT transmitted through breast milk could not be determined because the infants were receiving that drug directly.

The observed effect could represent a "two-for-one" deal, he said. "It's believed that maternal antiretroviral therapy decreases the risk of transmission to breast-feeding infants by reducing virus levels in the mother's breast milk. It now appears possible that the transmission risk may be reduced by breast-feeding because the infants are getting enough of the drugs directly," he said.

Additional studies are needed to determine whether exposure to the AIDS medications through breast milk alone will be risky for infants who have already acquired HIV in utero or during birth. "It may be that exposure to lower-than-therapeutic drug levels could cause resistance mutations to develop, potentially compromising future treatment," said Dr. Shapiro. It also is possible that exposed infants could develop toxicities from the antiretroviral drugs, including lowered blood counts, liver problems, or allergic reactions, he noted.

Dr. Shapiro reported that neither he nor his coinvestigators have a financial interest in the manufacturers of the drugs used in the study.

BY DIANA MAHONEY

New England Bureau