Related Experiment Video
Updated: Sep 15, 2025
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Fetal Defects in Mice Treated With Integrase Strand Transfer Inhibitors: Comparison of Dolutegravir, Raltegravir,
Haneesha Mohan1, Jessica Nguyen1, Audrey Yee1
1Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Background:
Integrase strand transfer inhibitors (INSTIs) are preferred for treatment of human immunodeficiency virus (HIV). However, safety data in pregnancy are limited for newer INSTIs.
Methods:
Pregnant C57BL/6 mice were randomly allocated to control (water), dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC), or cabotegravir (CAB) at clinically relevant doses, administered orally with tenofovir disoproxil fumarate and emtricitabine, once daily from gestational day (GD) 0.5 to sacrifice (GD 15.5). Fetuses were assessed for gross anomalies. Descriptive statistics were used to compare proportions of gross anomalies.
Results:
In total, 550 litters (115 in the control group, 150 for DTG, 113 for RAL, 79 for BIC, and 93 for CAB) were assessed. RAL was associated with the highest fetal weight, placental weight, and fetal-placental weight ratio (placental efficiency). Fetal weight, placental efficiency, and litter size were lowest in BIC and CAB. Neural tube defects were observed only in INSTI groups, with litter prevalence rates of 0.66% for RAL, 0.45% for DTG, 0.39% for BIC, 0.15% for CAB, and 0% for the control. Tail defects, eye defects, bleeding defects, cranial swelling, and growth restriction were significantly more common in all INSTI groups than in the control group. Overall rates of defects were lowest with DTG. Compared with the DTG group, limb and tail defects (indicative of spinal dysraphism) were significantly more prevalent in the RAL group, while bleeding defects were significantly more prevalent in the BIC and CAB groups.
Conclusions:
While INSTIs represent a critical advance in the management of HIV infection, the findings of the current study demonstrate a link between INSTI therapy and adverse fetal outcomes. This highlights the need for continued surveillance of pregnancy outcomes in women exposed to INSTIs.
