Combination antiretroviral drug therapy may reduce the risk of mother-to-child HIV transmission

Jul 29 2005

Two new studies support the hypothesis that combination antiretroviral drug therapy may reduce the risk of mother-to-child HIV transmission through breastfeeding, findings that could have significant implications in the developing world. Researchers in the first study found mothers pass antiretroviral medications on to their breastfeeding infants in concentrations high enough to prevent infection.

The second study showed levels of HIV RNA in breast milk are lower in mothers taking antiretroviral therapy than those who are not. Both studies appear in the September 1 issue of The Journal of Infectious Diseases, now available online.

Without antiretroviral therapy for an HIV-infected mother or her baby, transmission of HIV-1 through breast milk occurs in approximately 9 to 16 percent of breastfed infants. In the developing world, many HIV-infected mothers breastfeed rather than use formula due to the high cost of formula, lack of a safe water supply, and cultural norms.

Roger L. Shapiro, MD, MPH, of the Harvard School of Public Health, led the research in Botswana. In the first study, the researchers measured the concentrations of three antiretroviral drugs, nevirapine, lamivudine, and zidovudine, in the blood and breast milk of 20 HIV-infected women, and in the blood of their uninfected breastfeeding infants. All of the mothers had been receiving this combination of antiretroviral therapy continuously for at least six weeks prior to the start of the study, and all of the infants received a single dose of nevirapine and continuous zidovudine therapy after birth.

At either two or five months after delivery, all three drugs taken by the mothers were found in breast milk in concentrations similar to or higher than those found in the mothers' blood. In samples of the infants' blood, the investigators observed high, inhibitory concentrations of nevirapine that were above those thought necessary to protect against HIV infection. Dr. Shapiro and colleagues hypothesized that the presence of antiretroviral drugs in breast milk may reduce mother-to-child transmission through either direct inhibition of HIV replication in the breast milk, or by preventing infection from taking hold in the infant.

The high drug concentrations raised the possibility of some risks, as well as benefits, however. Such levels may be high enough to cause adverse effects associated with the drugs, such as rash, neutropenia, and anemia, and to lead to the emergence of drug-resistant virus.

For the second study, the researchers examined the ability of combination antiretroviral therapy to reduce HIV-1 RNA and DNA levels in breast milk. They measured these levels in two groups: 26 women who received nevirapine, lamivudine, and zidovudine beginning during pregnancy or postpartum, and 25 women from an earlier time period with comparable HIV disease, who did not receive antiretroviral therapy because it was unavailable to them at the time they were breastfeeding.

The results indicated that antiretroviral therapy suppresses HIV RNA in breast milk and may therefore reduce mother-to-child transmission of HIV during breastfeeding. Eighty-eight percent of the women receiving antiretroviral therapy had fewer than 50 copies/ml of HIV-1 RNA in their breast milk, compared with 36 percent of the women not taking therapy. This represents a statistically significant difference.

However, there was no such difference for HIV-1 DNA, which some studies suggest also contributes to mother-to-child transmission. One possible explanation for this lack of association between antiretroviral therapy and HIV DNA levels, the investigators hypothesized, may be the short duration of treatment in the study (a median of 98 days). Combination antiretroviral therapy may reduce HIV DNA in breast milk more slowly than HIV RNA, thus raising the risk that, when treatment duration is short, HIV DNA-associated transmission may occur despite the use of therapy.

Dr. Shapiro and colleagues concluded, "As drug costs decrease, maternal antiretroviral therapy may be a realistic strategy to maximize prevention of mother-to-child transmission in areas where formula feeding is not safe or feasible."

In an accompanying editorial, Marc Bulterys, MD, PhD, of the Centers for Disease Control and Prevention, agreed. "These studies are of vital importance for both biologic understanding and health policy. In the United States and other settings where HIV-infected mothers can safely avoid breastfeeding, the rate of mother-to-child transmission can be reduced to 1 percent or less. The goal in resource-limited settings, where HIV-infected women may by necessity opt to breastfeed, is to achieve similarly low transmission rates."