First trimester exposure to retrovir was associated with congenital heart defects, according to results of the ANRS-EPF French Peri-natal Cohort and the nested PRIMEVA randomised trial. “Our results suggest that zidovudine should be added to the list of drugs which, when administered in the first trimester of pregnancy, are associated with an increased risk of heart defects,” the researchers say in a Healio report. “The functional myocardial changes should also encourage us to pursue the study of potential long-term toxicity, including the potential role of cumulative in utero exposure to zidovudine.”
Since 1986, EPF has prospectively enrolled pregnant women with HIV who delivered their babies at 90 centres in France. EPF also collected follow-up data on those children through age 2. A paediatric cardiologist reviewed all congenital heart defect (CHD) cases. All patients in the PRIMEVA trial who had at least one echocardiogram were included in this analysis.
The main EPF analysis included 12,888 children. Exposure to retrovir (zidovudine, ViiV Healthcare) during the first trimester was associated with CHD (P < .001). Exposure to zidovudine was significantly associated with non-ventricular septal defect (VSD), non-atrial septal defect (ASD) CHD (adjusted OR = 2.4; 95% CI, 1-5.9) and also for VSD (aOR = 2.2; 95% CI, 1.4-3.5). CHD prevalence was greater in girls than boys (1.1% vs. 0.8%; P = .06).
In the PRIMEVA trial, 53 patients underwent echocardiograms at age 1 month, and 42 underwent the test at age 1 year. In this group, girls exposed in utero to the triple therapy Combivir (lamivudine/zidovudine, ViiV Healthcare) and Kaletra (lopinavir/ritonavir, AbbVie) had greater left ventricular (LV) shortening fraction and LV ejection fraction at 1 month. At 1 year, they also showed increased posterior wall thickness compared with patients assigned lopinavir/ritonavir monotherapy, the researchers wrote.
“Clinical implications of these results remain uncertain,” the investigators said. “Most of the CHD observed were minor defects. In particular VSD may require only a closer follow-up of the child, but this can be difficult in resource-limited settings and thus have more important consequences. The clinical significance of the differences in cardiac function observed here is also unknown.”
More research is necessary to determine which drug combinations will be the least toxic for the pregnancy and the newborn, the researchers concluded.