Abstract
Long-acting injectable antiretroviral therapy (LA-ART) using cabotegravir and rilpivirine is an emerging strategy to address adherence challenges among people with HIV. Data regarding safety and pharmacokinetics in pregnancy remain extremely limited. We describe a 29-year-old woman who maintained viral suppression throughout pregnancy while continuing long-acting cabotegravir/rilpivirine injections.
Introduction
Pregnancy presents unique challenges for HIV management due to physiologic changes and potential alterations in drug pharmacokinetics. Long-acting injectable cabotegravir and rilpivirine (CAB/RPV) offer an adherence-friendly alternative to daily oral regimens, but data on use during pregnancy are lacking. We report the successful use of CAB/RPV LA throughout pregnancy in a patient with longstanding adherence barriers to oral antiretroviral therapy (ART).
Background
Limited information is available regarding the use of cabotegravir (CAB) and rilpivirine (RPV) during pregnancy. Long-acting cabotegravir and rilpivirine (CAB + RPV LA) should only be used during pregnancy when the potential benefits outweigh the potential risks.¹
Among 25 pregnancies reported during phase II and III clinical trials of CAB + RPV LA, there were 10 live births and 15 non-live births.² Of the live births, nine were term and one was preterm at 36 weeks. Among the non-live births, there were eight elective abortions, five first-trimester spontaneous abortions, one second-trimester spontaneous abortion, and one ectopic pregnancy. One congenital anomaly (ptosis) was reported among the live births.²
A real-world, multicenter retrospective study of 31 pregnant individuals prescribed CAB + RPV LA in the United States between January 2021 and April 2024 provided additional insights.³ The median age at delivery was 29 years, and 81 percent of participants were Black/African American. Most patients (74%) were receiving CAB + RPV LA prior to pregnancy, with 61 percent on every-two-month dosing. Seven patients switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) during pregnancy, while eight initiated CAB + RPV LA (all monthly) during pregnancy at a median gestational age of 22 weeks. Viral suppression was generally maintained throughout pregnancy, and there were 28 live births, two spontaneous abortions, and one stillbirth reported. Data on congenital abnormalities were not reported.³
The Antiretroviral Pregnancy Registry (APR) reported data on 43 outcomes (42 pregnancies), which included 35 live births (one twin birth), one stillbirth, three spontaneous abortions, and four induced abortions.⁴
A maternal-fetal physiologically based pharmacokinetic (PBPK) model predicted reductions in plasma CAB and RPV concentrations when initiated during the second and third trimesters of pregnancy.⁵ Despite these reductions, predicted levels remained above efficacy thresholds.
An ongoing phase IV study, IMPAACT 2050, is designed to further characterize the pharmacokinetics of long-acting CAB and RPV in women with HIV during pregnancy and postpartum. Participants will be followed through pregnancy and, together with their infants, through six weeks postpartum.
Case Presentation
A 29-year-old woman diagnosed with HIV in 2015 had persistent difficulties adhering to oral ART due to nausea, vomiting, and a gagging sensation while swallowing pills. Her adherence issues were exacerbated during pregnancy. She is gravida 6, para 4, abortus 1 (G6P4A1) and has delivered four HIV-negative children by cesarean section. Records show that she had poor adherence to oral ARVs during her previous pregnancies with frequent complaints of nausea. She had HIV viremia at the time of delivery in 2016 and has shown HIV viral loads between 9,000 and 18,000 between 2019 and 2023. This overlaps with the timing of three additional deliveries in 2018, 2019, and 2022.
On April 12, 2023, her plasma HIV RNA was 13,700 copies/mL, and her CD4 T-cell count was 343 cells/µL (nadir 277 in September 2022). She was initiated on long-acting CAB/RPV (cabotegravir 600 mg + rilpivirine 900 mg intramuscularly every eight weeks) following published protocols for virologically suppressed adults.¹˒² By July 2023, her HIV RNA became undetectable and has remained suppressed thereafter.
On January 21, 2025, she presented at 11 weeks of gestation after confirming pregnancy. Her most recent viral load (September 27, 2024) was undetectable. She expressed interest in continuing injectable therapy due to her intolerance of oral medications. After multidisciplinary review and with reference to NIH perinatal HIV treatment guidance, she continued on CAB/RPV.³ She received the higher-dose eight-week regimen at the visit on January 21, 2025. Due to concern for lower drug levels between eight-week injections, her doses were adjusted to monthly injections (cabotegravir 400 mg + rilpivirine 600 mg) starting March 25, 2025.
A pharmacokinetic sample was obtained June 5, 2025 (27 weeks’ gestation). CAB and RPV concentrations were quantified using previously described methods.6 The CAB (1545 ng/mL) and RPV (72.9 ng/mL) concentrations were 44.8 percent and 15.0 percent lower than predicted mean trough concentrations from the FLAIR and ATLAS studies, respectively.¹˒² However, both concentrations remained above the PAIC₉₀ (CAB 166 ng/mL; RPV 12 ng/mL) and above the more conservative 4×PAIC₉₀ thresholds (CAB 664 ng/mL; RPV 48 ng/mL). No injection-site or systemic adverse events were reported.
Outcome and Follow-Up
At 38 weeks’ gestation (July 25, 2025), she delivered a healthy female infant via cesarean section. Birth weight was 2590 grams, with Apgar scores of 8 and 8. Maternal HIV RNA at delivery was undetectable. The infant received zidovudine prophylaxis (4 mg/kg twice daily) for four weeks per national perinatal guidelines.³ The infant had an HIV RNA PCR test on August 19, 2025, which was negative. The mother chose formula feeding. The infant has missed three follow-up visits but was scheduled for reassessment in December 2025.
Discussion
This case illustrates the potential role of long-acting CAB/RPV in maintaining viral suppression during pregnancy when adherence to oral ART is not possible. Although cabotegravir and rilpivirine levels were moderately lower than expected, concentrations remained within therapeutic ranges, and viral suppression was preserved. These findings align with early pharmacokinetic trends observed in other studies, suggesting decreased but still adequate exposures during pregnancy.¹˒²
Ongoing research, including the IMPAACT 2050 study, is investigating the pharmacokinetics and safety of long-acting CAB/RPV in pregnant and postpartum individuals.⁵ Until these data are available, decisions regarding continuation of long-acting therapy during pregnancy should be individualized, balancing adherence risks and potential pharmacokinetic variability.³˒⁵
Conclusion
Long-acting CAB/RPV therapy maintained viral suppression throughout pregnancy in this patient with severe oral medication intolerance. Although concentrations were lower than predicted trough levels, they remained above efficacy thresholds. LA-ART may represent a viable alternative for select pregnant patients with adherence barriers, warranting further study.
