The study, a combined analysis of 7 studies of U.S. pregnant women with HIV, appears in the June 13, 2002 issue of the New England Journal of Medicine. The study was funded by the National Institute of Child Health and Human Development (NICHD) and the National Institute of Allergy and Infectious Diseases (NIAID). The study was conducted by researchers at NICHD, NIAID, and several academic and medical institutions.

The U.S. researchers undertook the study in response to an earlier Swiss study that showed that HIV positive women who took a combination of anti HIV drugs that included protease inhibitors were more likely to give birth prematurely than were HIV positive women who did not take protease inhibitors.

"Combination therapy has proven invaluable in preventing the transmission of HIV from mother to child," said Duane Alexander, M.D., Director of the NICHD. "This study did not find any association between combination therapy and several adverse pregnancy outcomes. However, a small association between combination therapy with protease inhibitors and very low birth weight needs to be investigated further."

Very low birth weight infants are at increased risk for infant death and disability. Although they account for only 1 percent of all births in the United States, they account for over 40 percent of infant mortality. Very low birth weight infants who do survive often require lengthy and expensive intensive care treatment.

There are three categories of drugs used to treat HIV infection. Reverse transcriptase inhibitors, including the nucleoside and non-nucleoside categories, interfere with an enzyme called reverse transcriptase, which the virus needs to make copies of itself. Protease inhibitors interfere with the enzyme protease, which allows HIV to infect cells. Forms of anti-HIV therapy include giving only one reverse transcriptase inhibitor at a time (monotherapy), a combination or two or more reverse transcriptase inhibitors (combination therapy), and a combination of reverse transcriptase inhibitors and protease inhibitors (combination therapy with protease inhibitors). Combinations of anti-HIV drugs have been shown to reduce the likelihood of a mother passing the virus on to her child.

In their study, the researchers analyzed data from 7 large studies of pregnant women with HIV-1 infection to assess their risk of giving birth prematurely as well as other adverse outcomes of pregnancy. In all, 3266 women who delivered their infants from 1990 through 1998 were included in the study. Of these, 1590 received only one anti-HIV drug (not a protease inhibitor) another 396 women received a combination of drugs that did not include a protease inhibitor, 137 received a combination of anti-HIV drugs that included a protease inhibitor, while 1143 did not take any anti HIV drugs.

None of the infants in any of the groups receiving any type of HIV treatment were at any greater risk for such adverse outcomes as premature birth, low birth weight (between 1500 and 2500 grams), still birth, or low Apgar scores than were infants in the group that did not receive any anti-HIV treatments. The Apgar test is used to estimate a baby's general condition at birth, measuring such characteristics as heart rate, breathing and muscle tone.

The rate of premature delivery was similar for women who received anti retroviral drugs (16 percent) and for those who did not (17 percent). Moreover, therapy with a combination of antiretroviral drugs did not appear to increase the risk of preterm delivery when compared to use of only one antiretroviral drug. The rates of low Agar scores and stillbirths were also similar for the two groups. Of the 137 women who received combination therapy with protease inhibitors, 7 had infants with very low birth weight (5 percent), compared with 9 women (2 percent) who received combination therapy without protease inhibitors.

"Our data provide reassurance that the risks of adverse outcomes of pregnancy that are attributable to antiretroviral therapy are low and are likely to be outweighed by the recognized benefits of such therapy during pregnancy," the study authors wrote.

The NICHD is part of the National Institutes of Health, the biomedical research arm of the federal government. The Institute sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Clearinghouse, 1-800-370-2943; e-mail NICHDClearinghouse@mail.nih.gov.