Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States

Capsid Inhibitors

Lenacapavir (LEN)

Summary

• Pharmacokinetic (PK) data are insufficient to make dosing recommendations for oral or long-acting injectable lenacapavir (LEN) during pregnancy or breastfeeding.
• Clinical data are insufficient to characterize the risk for congenital anomalies associated with in utero exposure to LEN. No reproductive toxicity or teratogenicity concerns were identified in animal studies.
• LEN is U.S. Food and Drug Administration (FDA) approved for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection whose current antiretroviral (ARV) regimen is failing due to resistance, intolerance, or safety considerations.
• LEN is under evaluation for HIV pre-exposure prophylaxis (PrEP); LEN is not FDA approved for HIV prevention. 
   

Human Studies in Pregnancy

Pharmacokinetics

No data are available on the PK of LEN with continuing subcutaneous (SQ) injections during pregnancy.

Placental and Breast Milk Passage

No data are available regarding placental transfer of LEN. Additionally, no data are available describing breast milk passage of LEN in humans; because LEN is more than 98.5% protein bound, amounts found in breast milk are likely low.¹

Teratogenicity/Adverse Pregnancy Outcomes

The Antiretroviral Pregnancy Registry (APR) provides updated birth defect data for LEN and other ARV drugs twice a year through an interim report released in June and December. The APR has not monitored sufficient numbers of first-trimester exposures to LEN to report on the risk of overall birth defects.

In the PURPOSE 1 study², a Phase 3, double-blind, randomized controlled trial of adolescent girls and young women in South Africa and Uganda, participants were assigned to receive twice-yearly SQ LEN versus daily oral emtricitabine (FTC) plus tenofovir alafenamide (TAF) or daily oral FTC plus tenofovir disoproxil fumarate (TDF; active control) for HIV PrEP. At the time of the interim analysis, there were 510 pregnancies among 487 participants—193 in the LEN group, 219 in the FTC/TAF group, and 98 in the FTC/TDF group—with 277 delivery outcomes and 233 ongoing pregnancies. Pregnancy outcomes were similar to those expected for the general population. No documented incident HIV was reported among participants receiving LEN (see PrEP to Prevent HIV During Periconception, Antepartum, and Postpartum Periods).

Animal Studies

Carcinogenicity

LEN was not mutagenic in a series of in vitro and animal in vivo genotoxic assays; LEN was not carcinogenic in a mouse model.³

Reproduction/Fertility

In rats, no effects on fertility, mating performance, or early embryonic development were observed at LEN exposures 5 times greater than the exposure in humans at recommended doses.³

Teratogenicity/Adverse Pregnancy Outcomes

No significant toxicological effects on embryo-fetal development in rats and rabbits or pre- and postnatal development in rats were observed at area under the curve drug exposures approximately 16 times (rats) and 39 times (rabbits) the exposure in humans at recommended doses.²

Placental and Breast Milk Passage

LEN was detected at low levels in the plasma of nursing rat pups.³

Excerpt from Table 14

References

1. National Institute of Child Health and Human Development. Lenacapavir. Drugs and Lactation Database (LactMed(R)). 2023. Available at: https://pubmed.ncbi.nlm.nih.gov/36701515.
2. Bekker LG, Das M, Abdool Karim Q, et al. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. N Engl J Med. 2024. Available at: https://pubmed.ncbi.nlm.nih.gov/39046157.
3. Sunlenca (lenacapavir) package insert [package insert]. Food and Drug Administration. 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf.