Is Antiretroviral Therapy during Pregnancy Associated with an Increased Risk of Preterm Delivery, Low Birth Weight or Stillbirth?

In most developed countries antiretroviral therapy (ART) is recommended to pregnant women in order to lower the risk of mother-to-child transmission of HIV and to improve the health of the mother. Despite information gleaned from a number of prior studies, the optimal HAART regimen that would provide the most benefit and the least toxicity to both mother and ART has not yet been determined.

Data on ART-related complications during pregnancy are scant. However, in the largest evaluation conducted in the US to date of the risks of adverse pregnancy outcomes associated with ART, Tuomala et al. reported on 2123 HIV-infected women enrolled in 7 clinical studies who received some form of ART and 1143 women who did not receive any [1].

Both groups had similar rates of low preterm birth, and low-birth-weight infants. After adjustment for various risk factors, combination ART was not associated with an increased risk of preterm delivery or low birth weight, compared with monotherapy.

The objective of the present study was to investigate whether ART was associated with adverse pregnancy outcome at a single site managed by maternal-fetal medicine subspecialists adhering to strict protocols and unified standards of care.

Using prospectively gathered data, women were identified who were determined to be HIV positive before or during pregnancy who sought care at our prenatal clinic and who gave birth at the University of Miami/Jackson Memorial Medical Center from 1990 through 2002. The outcome measures were preterm delivery, low birth weight, and stillbirth.

Results

The cohort included 999 women who received antiretroviral therapy during pregnancy (monotherapy in 492, combination therapy without a protease inhibitor [PI] in 373, and combination therapy with a PI in 134) and 338 women who did not receive therapy.

After adjustment for possible confounders, only combination therapy with a PI was associated with an increased risk of preterm delivery, compared with any other.

There were no differences in rates of low birth weight and stillbirth, regardless of therapy.

In conclusion, the authors write, "Compared with monotherapy and combination therapy without a PI, only combination therapy with a PI was associated with an increased risk of preterm delivery."

Commentary

According to the study authors, this is the largest single-site study and the only large study reported to date that can account for both the completeness of its data and its management protocols and is representative of HIV-infected pregnant women in the United States. In addition, the study is a unique one due to its management by a team of maternal-fetal medicine experts.

"It is reassuring," write the authors, "to find that the risks of adverse pregnancy outcomes attributable to ART are small and likely to be outweighed by the known benefits of such therapy in pregnancy."

However, the authors emphasize that the decision to use a protease inhibitor (PI) during pregnancy "should be made with caution" and they point to the importance of "counseling patients about the risks of prematurity before the initiation of therapy."

See also the editorial on PI use during pregnancy by Tuomala and Yawetz in the May 1, 2006 issue of The Journal of Infectious Diseases [2].

References

1. R E Tuomala, D E Shapiro, L M Mofenson, and others. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. New England Journal of Medicine 346: 1863-1870. 2002.

2. R E Tuomala and S Yawetz. Protease Inhibitor Use During Pregnancy: Is There an Obstetrical Risk? New England Journal of Medicine 346: 1191-1194. May 1, 2006.

Source
A M Cotter, A G Garcia, M L Duthely, and others. Is Antiretroviral Therapy during Pregnancy Associated with an Increased Risk of Preterm Delivery, Low Birth Weight, or Stillbirth? The Journal of Infectious Diseases 193(9):1195-1201 May 1, 2006.