Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States

Integrase Inhibitors

Bictegravir (BIC)

Animal Studies

Carcinogenicity
Bictegravir (BIC) has not been shown to be genotoxic or mutagenic in vitro.¹

Reproduction/Fertility
BIC did not affect fertility, reproductive performance, or embryonic viability in male and female rats at exposures (based on area under the curve [AUC]) that were 29 times higher than those observed in humans who received the recommended dose.¹

Teratogenicity/Adverse Pregnancy Outcomes
No adverse embryo-fetal effects were observed in rats and rabbits at BIC exposures (based on AUC) of up to about 36 times (in rats) and 0.6 times (in rabbits) the exposures observed in humans who received the recommended dose. Spontaneous abortion, increased clinical signs (e.g., fecal changes, thin body, cold-to-touch), and decreased body weight were observed in rabbits at a maternally toxic dose (i.e., 1,000 mg/kg per day, which produced an exposure approximately 1.4 times higher than the exposure observed in humans who received the recommended dose).¹

Placental and Breast Milk Passage
No data are available on placental passage of BIC. In a pre- and postnatal development study conducted in rats, BIC was detected in the plasma of nursing rat pups on postnatal Day 10, likely due to the presence of BIC in milk.¹

Human Studies in Pregnancy

Pharmacokinetics
No pharmacokinetic studies of BIC in pregnant women have been reported.

Placental and Breast Milk Passage
No pharmacokinetics studies of BIC in pregnant women have been reported.

Teratogenicity/Adverse Pregnancy Outcomes
The Antiretroviral Pregnancy Registry has prospectively monitored 40 pregnancies in women treated with BIC during periconception or pregnancy, including 25 infants with periconception exposure, 3 infants with later first-trimester exposure, and 12 infants with exposure in the second or third trimester. No cases of birth defects have been reported to date, but these data are insufficient to make conclusions regarding the safety of BIC during pregnancy.²

Excerpt from Table 10

Note: When using FDCs, refer to other sections in Appendix B and Table 10 for information about the dosing and safety of individual drug components of the FDC during pregnancy.

References

1. Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide fumarate) [package insert]. Food and Drug Administration. 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210251s006lbl.pdf.
2. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral pregnancy registry international interim report for 1 January 1989–31 January 2020. Wilmington, NC: Registry Coordinating Center. 2020. Available at: http://www.apregistry.com/.