January 2015 

ART during pregnancy found safe for babies’ hearts

As mentioned before in this issue of TreatmentUpdate, the use of potent combination anti-HIV therapy (commonly called ART or HAART) along with other measures can significantly help pregnant HIV-positive women give birth to healthy, HIV-negative babies.

Researchers are continuing to monitor the health of babies born to HIV-positive mothers to assess the safety of ART. In one such study, researchers at Wayne State University in Detroit collaborated with scientists in other parts of the U.S. to assess any potential ART-related injury or birth defects in infants. Reassuringly, they found no evidence of toxicity to the heart in children born to HIV-positive mothers who used ART during pregnancy. However, they appear to have found a possible signal of subtle changes to the thickness of the heart’s pumping chambers in some of these children. This latter finding needs to be treated with caution and we explain why in this report.

Study details

Researchers from 22 clinics across the U.S. that cared for infants born to HIV-positive mothers pooled their data and analysed it, seeking statistical relationships between any potential signals of birth defects or injury to the heart and potential factors that may have caused such problems. They assessed the heart health of the infants by using ultrasound scans. One ultrasound scan was done per child.

For their study, researchers gathered and compared data between 2007 and 2012 from the following two groups of infants:

  • 411 HIV-negative infants born to ART-using women
  • 98 HIV-negative infants whose mothers were also HIV negative


The researchers found a statistical signal that suggested that fetal exposure to the drug AZT (zidovudine, Retrovir and in Combivir and Trizivir) may have resulted in a very subtle change to the shape of part of the heart. The net result of this would be that slightly more physical stress would be applied to the walls of the heart by the flow of blood.

Points to consider

1. Perhaps the most important finding is that researchers did not find any clinically significant injury of the hearts of HIV-negative children born to HIV-positive mothers; that is, the hearts were functioning normally.

The researchers did appear to find some very subtle changes to the hearts of children, which, in their words, “could be at least partially explained by [exposure to ART in the womb].” Readers should note that the researchers’ statement contains uncertainty; that is, they are not sure what role ART played in their findings. Furthermore, the present study is observational in nature; such studies are good at finding associations between a drug and an outcome but cannot prove cause and effect. In other words, the present study cannot discriminate between the potential effect of ART in the womb and the effect of HIV in the womb. Thus this study’s findings must be treated with caution and require verification in another study.

2. Several factors are associated with very subtle changes to the shape of the heart’s pumping chambers. For instance, in the present study, researchers found that the use of tobacco and/or alcohol during pregnancy resulted in changes in the hearts of infants as follows:

  • the pumping ability of the heart was weakened
  • the walls of the heart became thicker

These effects were independent of the use of ART.

Also, in the time before ART was available in high-income countries (before 1996), researchers found that HIV-infected children commonly developed enlarged hearts. Complications arising from enlarged hearts and cardiac dysfunction were reported in HIV-positive children before 1996.

It is possible that there are other causes for the subtle cardiac issue seen in the current study. For instance, the U.S. researchers suggested that chronic low-level inflammation in the womb, triggered by the mother’s HIV infection, might be a culprit. Previous research with HIV-negative children born to HIV-positive mothers suggests that some of these children may have elevated levels of inflammation in their cardiovascular system despite being born HIV negative.

3. To cast some clarity on the issue, robustly designed studies are needed.  Such studies take time to create and operate and are relatively expensive. 

—Sean R. Hosein


  1. Wilkinson JD, Williams PL, Leister E, et al. Cardiac biomarkers in HIV-exposed uninfected children. AIDS. 2013 Apr 24;27(7):1099-108.
  2. Lipshultz SE, Williams PL, Zeldow B, et al. Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers. AIDS. Jan 2015;29:91-100.
  3. Bulterys M, Berry RJ, Watts DH. Preconception antiretroviral therapy and birth defects: what is needed? AIDS. 2014 Nov 28;28(18):2777-2780.