Most studies examining the association of prenatal antiretroviral exposures with congenital anomalies (CAs) in children born to HIV-infected women have been reassuring, but some suggest increased risk with specific antiretrovirals.
To evaluate associations of in utero antiretroviral exposures with CAs in HIV-exposed uninfected children.
prospective cohort study, the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study.
22 US medical centers
2580 HIV-exposed, uninfected children enrolled in SMARTT between 2007–2012.
First trimester exposure to any antiretroviral and to specific antiretroviral medications.
The primary endpoint was a CA, based on clinician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate associations of CAs with first trimester antiretroviral exposures, adjusting for demographic and maternal characteristics.
CAs occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI: 5.85–7.82%); there were 242 confirmed major CAs (72 musculoskeletal, 55 cardiovascular). The prevalence of CAs increased significantly in successive birth cohorts (3.8% for children born <2002 up to 8.3% for 2008–2010). In adjusted models, there was no association of first trimester exposures to any antiretroviral, to combination antiretroviral regimens, or to any drug class with CAs. No individual antiretroviral in the reverse transcriptase inhibitor drug classes was associated with increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir (adjusted odds ratio (aOR)=1.93, 95% confidence interval (CI):1.23,3.03) and for ritonavir used as a booster (aOR=1.52, 95%CI: 1.08,2.14). With first trimester atazanavir, risks were highest for skin and musculoskeletal CAs (aORs=5.24 and 2.55, respectively).
Conclusions and Relevance
Few individual antiretrovirals and no drug classes were associated with increased risk of CAs after adjustment for calendar year and maternal characteristics. While the overall risk remained low, there was a relative increase in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV use during pregnancy still outweigh such risks, although further studies are warranted.