The widespread use of antiretroviral therapy has led to a dramatic decrease in the rate of mother-to-child transmission (MTCT) of HIV.  Before 1994, MTCT rates in the U.S. were 20% to 25%; now rates of less than 2% are achieved with the use of HIV medications and elective cesarean section. It is estimated that between 6,000 and 7,000 HIV-positive women give birth and 144 to 236 babies acquire HIV infection each year in the U.S. 

While this is undoubtedly good news, there are also lingering concerns of safety.  Some reports from Europe have suggested that the use of antiretroviral therapy during pregnancy is associated with substantially increased rates of premature deliveries.  The risk was particularly pronounced for protease inhibitor (PI) use when started early in pregnancy or before conception.  Other studies, conducted in Europe and the U.S., have not shown such associations.

Many of the studies completed to date have suffered from limitations, such as small patient sample sizes.  In turn, the published evidence on the question of antiretroviral drug use during pregnancy and the risk of prematurity remains, to this day, controversial.  To provide some clarity, Athena Kourtis, MD, PhD, of the U.S. Centers for Disease Control and her colleagues conducted what is known as a “meta-analysis” of all the relevant studies published to date in order to derive – given a greatly expanded number of subjects – a more reliable estimate of the association between antiretroviral therapy use during pregnancy and premature deliveries.

A total of 14 published papers involving MTCT research conducted in the U.S. and Europe were reviewed. 

Generally speaking, Dr. Kourtis’ team’s meta-analysis found that antiretroviral therapy was not associated with an increased risk of premature delivery. 

The researchers also examined particular types of therapy used by the women during the studies.  Premature births were no more common among HIV-positive women who took monotherapy – for example, Retrovir® (zidovudine) without other HIV medications – than those who didn’t receive any antiretroviral therapy at all.  What’s more, there was no statistically significant difference in premature birth rates between women who took combination antiretroviral therapy compared to those who took monotherapy or no treatment during pregnancy. 

When compared with no antiretroviral therapy, the use of PI-based regimens did not result in a statistically significant increased risk.  However, when women taking PI-based regimens were compared to those taking non-PI-based regimens (e.g., regimens using a non-nucleoside reverse transcriptase inhibitor) there was a slight increase in the risk of premature delivery. 

Only a few studies reported the time of initiation of combination antiretroviral therapy in pregnancy.  For those that did, the risk of premature delivery was found to be slightly increased among women who began treatment before becoming pregnant or during the first trimester (the first three months of pregnancy), compared with initiation of treatment during the second or third trimester.

“This meta-analysis concurs with previously published U.S. findings that antiretroviral regimens currently being used to treat HIV-infected women during pregnancy are not associated with an increased risk of premature delivery on a population basis,” Dr. Kourtis and her colleagues write.  However, the researchers suggest that additional studies are necessary are evaluate the risk of prematurity among different ethnic and geographical populations of pregnant HIV-infected women treated with different types of antiretroviral regimens.  “As antiretroviral regimens become increasingly complex and as newer agents are introduced, such analyses will be important for ensuring that antiretroviral regimens continue to provide optimal health benefits for both mothers and their infants.”

Source:

Kourtis AP, Schmid CH, Jamieson DJ, et al. Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis. AIDS 21(5):607-15, 2007.