Study results appear to indicate that conceiving while on ART poses a greater risk of stillbirth and miscarriage; however, further analysis revealed a lack of association between ART & poor outcomes.
As a lifesaving measure, antiretroviral therapy (ART) is recommended for people who have HIV, including pregnant women. Women who are infected with HIV during pregnancy and forgo treatment are putting the fetus at great risk of infection during gestation or birth (or afterward if the baby is breastfeeding.) As crucial as it is for expectant mothers and their babies, can ART itself pose a risk of miscarriage or stillbirth?
To find out, a team of scientists from the David Geffen School of Medicine at the University of California, Los Angeles; the Harvard T. H. Chan School of Public Health in Boston; the Icahn School of Medicine at Mount Sinai in New York; the Division of AIDS at the National Institute of Allergy and Infectious Disease; and various other locations around the United States and the world conducted an analysis of women who were involved in the “HAART (highly active antiretroviral therapy) Standard” part of the Promoting Maternal and Infant Safety Everywhere (PROMISE HS) trial.
This trial followed 1652 HIV-positive women in 8 countries whose CD4 plus T-cell counts were at least 400 cells/mm3 within 120 days of starting ART while pregnant. The women were randomized to either continue or discontinue ART within 42 days of giving birth. Those women who discontinued ART were instructed to restart the therapy if it was medically warranted, such as if their CD4 plus T-cell count dropped significantly, or if they became pregnant again.
Seventeen percent of the study subjects (277) became pregnant again and recorded pregnancy outcomes were available for 266 of them. Thirty-three women out of 140 (23.6%) who had continued ART experienced a miscarriage or stillbirth compared with 15 out of 126 (11.9%) who had discontinued ART. However, when doing an as-treated analysis, the difference in the percentages of women who experienced a miscarriage or stillbirth was no longer significant.
The type of ART regimen that a woman follows may have some impact on a pregnancy. The scientists found that for women who had continued ART after a pregnancy and conceived again, the relative risk for a poor outcome was higher in those who were on non-nucleoside reverse-transcriptase inhibitors (NNRTIs) compared with those on protease inhibitors; however, there were only 12 women on NNRTIs in this cohort.
On its surface, the study appears to bolster the hypothesis that taking ART during pregnancy can pose a risk, but the as-treated analysis of the data does not support that hypothesis. Also, there is a bigger picture to consider. “While these results may signal the possibility of an increase in adverse outcomes for women who conceive on ART, the relatively low rates of adverse pregnancy outcomes must be weighed against the tremendous benefit of lifelong, uninterrupted ART,” the authors wrote in the discussion section of the study.
The study did have a few limitations, including missing data on pregnancy outcomes for 11 subjects. The authors admitted that it is possible certain women did not reveal abortions they may have had, allowing them to be classified as miscarriages. The researchers also did not ask the subjects about difficulties they may have had during prior pregnancies that could have affected their ability to carry to term and deliver in subsequent pregnancies. “More data are needed on pregnancy outcomes among women who conceive on ART, particularly with newer regimens,” the authors concluded.