Long-acting injectable cabotegravir/rilpivirine in a pregnant woman living with HIV with hyperemesis gravidarum:a case report and review of literature

Introduction

Sustained virological suppression throughout pregnancy is essential to prevent vertical transmission of HIV. Adherence to daily oral antiretroviral therapy (ART) can be compromised by several factors, including social vulnerability, side effects, and pregnancy-specific conditions such as hyperemesis gravidarum (HEG). HEG, affecting up to 3% of pregnancies, can impair both drug intake and gastrointestinal absorption, potentially leading to virological failure in the absence of drug resistance. Long-acting injectable cabotegravir/rilpivirine (CAB/RPV LA), approved for maintenance therapy in virologically suppressed non-pregnant adults, bypasses gastrointestinal absorption and requires administration only every one or 2 months, representing a potentially transformative option for individuals with adherence barriers. The recently published LATITUDE trial demonstrated, for the first time in a randomised controlled setting, the superiority of CAB/RPV LA over oral ART in reducing regimen failure among people with HIV and significant adherence challenges. ¹ However, its use in pregnancy remains off-label, and current guidelines do not recommend its initiation during pregnancy owing to limited PK, safety and clinical outcome data. ² We report a case of successful use of CAB/RPV LA as rescue therapy initiated during active viraemia in pregnant person living with HIV with treatment failure due to HEG, and provide a focused review of the available literature.

Case report

A 26-year-old woman from Ghana living with HIV-1 (subtype CRF02_AG, diagnosed in 2012) was referred to our Unit in October 2023 after a prolonged period of loss to follow-up. She had a complex history of social vulnerability, poor adherence, and multiple ART changes for inadequate efficacy and reported side effects over the preceding decade. At that visit, CD4 + T-lymphocyte count was 243 cells/mm³ and HIV RNA was 172,304 copies/mL. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide was initiated, but the person was again lost to follow-up after 3 months.

She re-presented in October 2025 with advanced immunosuppression (CD4+ 168 cells/mm³, HIV RNA 87,794 copies/mL). Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was initiated. By December 2025, HIV RNA had declined to 6577 copies/mL and the person disclosed she was pregnant (approximately 20 weeks of gestation). At gestational week (GW) 24, HIV RNA was 29 copies/mL. However, between GW 24 and 28, the person reported severe nausea and vomiting particularly following ART intake. At GW 28, HIV RNA had rebounded to 57,950 copies/mL. At the time of the switch, body weight was 63 kg and height 152 cm (BMI 27.3 kg/m²). . Resistance testing at the time of switching confirmed the absence of resistance-associated mutations to cabotegravir or rilpivirine, supporting hypothesis that failure was due to non-adherence and impaired absorption rather than virological resistance.

Given the inability to tolerate oral ART, a multidisciplinary decision was made to initiate CAB/RPV LA. Intramuscular injections of cabotegravir 600 mg/rilpivirine 900 mg were administered at GW 29 (2 March 2026) and after 4 weeks (31 march 2026) GW 33. Virological suppression (<20 copies/mL) was achieved within 4 weeks of the first injection. At GW 36, an elective caesarean section was performed with intravenous zidovudine prophylaxis and post-partum neonatal prophylaxis with zidovudine syrup for 4 weeks. A healthy male neonate was delivered with no evidence of HIV infection on subsequent testing. In the post-partum, the person continued on every 2 months intramuscular injections CAB/RPV (cabotegravir 600 mg/rilpivirine 900 mg) becasue,in our hospital, only this formulation is available. The third injection was made on 26 may 2026. On the same day blood examination showed a CD4 + cells count of 342/cells/mm³ with HIV RNA <20 copies/ml. No adverse maternal or neonatal outcomes were observed during the follow-up period. As the infant is currently less than 3 months of age, definitive exclusion of vertical transmission cannot yet be confirmed; however, all HIVRNA testing performed to date has been negative.

Discussion and conclusions

To our knowledge, this is one of the first reported cases of CAB/RPV LA initiated during active viraemia as rescue therapy in pregnancy. Unlike previously published cases, in which CAB/RPV LA was continued from a pre-pregnancy regimen or initiated in virologically suppressed individuals, our case presented with a significant viral rebound due to HEG-mediated treatment failure, without evidence of acquired drug resistance. This distinction is clinically important: it identifies HEG as a specific and potentially underrecognised indication for switching to long-acting injectable ART in pregnancy. It should be noted, however, that this person also had a longstanding history of social vulnerability and poor adherence predating the pregnancy; while HEG was the proximate trigger for virological rebound in this episode, broader social determinants of health likely contributed to their overall adherence challenges and should not be overlooked in clinical management.

The available literature on CAB/RPV LA in pregnancy consists predominantly of case reports, case series and modelling studies. Patel et al. reported the largest dataset from ViiV Healthcare-sponsored trials and a compassionate use programme: among 25 pregnancies with exposure to CAB/RPV LA, 10 resulted in live births; one case of congenital ptosis was reported, while the remaining nine neonates had no congenital anomalies documented. ³

Van der Wekken-Pas et al. reported a single case of bimonthly CAB/RPV LA continued throughout pregnancy, documenting a 70–75% reduction in rilpivirine concentrations compared with non-pregnant individuals, while cabotegravir levels remained comparable; no virological failure or vertical transmission occurred in this individual. ⁴

Rakhmanina et al. described a single case of off-label monthly high-dose CAB/RPV LA with therapeutic drug monitoring (TDM), observing higher post-partum concentrations (+56% CAB, +73% RPV) relative to early pregnancy (7 weeks), consistent with pregnancy-induced pharmacokinetic alterations. ⁵ A multicentre case series from Sunagawa et al. further documented successful use in several pregnant individuals with varying clinical indications. ⁶ Kazanji et al. recently described the first quantitatively documented case of substantial viral load reduction with LA CAB/RPV in the third trimester, with HIV-1 RNA falling from 16,600 to 171 copies/mL within 1 week of a single dose in person living with HIV unable to tolerate oral ART due to longstanding pill aversion, further supporting the role of injectable regimens when oral therapy is not feasible. ⁷

Physiologically-based pharmacokinetic (PBPK) modelling by Atoyebi et al. provided important mechanistic insights: monthly CAB LA was predicted to maintain trough concentrations above the target of 664 ng/mL throughout pregnancy, while bimonthly dosing fell below this threshold in approximately 0.5% of the pregnant population during the third trimester. Rilpivirine concentrations were more concerning: both monthly and bimonthly dosing were predicted to fall below the 50 ng/mL target in at least 40% and over 90% of the population, respectively. ⁸ These findings strongly support preference for monthly dosing in pregnancy and highlight RPV as the pharmacokinetically vulnerable component of the regimen.^9,10

This person achieved rapid virological suppression on the standard monthly initiation schedule, consistent with the available evidence. The successful prevention of vertical transmission in a context of active viraemia at initiation is a particularly noteworthy outcome. The use of adjunctive intravenous zidovudine at delivery, in line with current guidance for people with detectable viral load near term, likely contributed to this outcome.

Limitations include the absence of therapeutic drug monitoring, which would have allowed pharmacokinetic characterisation in this specific clinical context, and the brief postpartum follow-up period. The ongoing IMPAACT 2040 (CREATE) study and the IMPAACT 2050 Phase IV trial are expected to provide prospective PK and safety data that will be essential to define optimal dosing and clinical indications in pregnancy.

In conclusion, CAB/RPV LA may represent a viable and rapidly effective rescue strategy in pregnant individuals when oral ART is not feasible, particularly in the context of HEG and other adherence issues. Monthly dosing should be preferred based on available PK data. TDM, shortened injection intervals, and close virological monitoring are advisable. This case adds to the growing body of evidence supporting expanded clinical evaluation of long-acting regimens in pregnancy.

CPD questions

1. What is the most likely mechanism of virological failure described in this case?

(a) Acquired integrase resistance mutations

Answer: (c) Virological rebound occurred in the absence of resistance-associated mutations and in the context of severe nausea and vomiting following ART intake, consistent with HEG-mediated impairment of oral drug absorption.

2. Based on available pharmacokinetic modelling data, which dosing schedule of long-acting CAB/RPV is most likely to maintain adequate drug concentrations throughout pregnancy?

(a) Bimonthly dosing of both cabotegravir and rilpivirine

Answer: (c) PBPK modelling predicts that monthly CAB LA maintains adequate trough concentrations throughout pregnancy, while bimonthly dosing of rilpivirine fails to achieve target levels in a significant proportion of pregnant individuals. Monthly dosing with therapeutic drug monitoring is therefore preferred.

3. What is the current regulatory status of CAB/RPV LA in pregnancy and what evidence gap must be addressed?

(a) It is approved for use in pregnancy based on Phase III trial data

Answer: (b) CAB/RPV LA use in pregnancy is currently off-label. Current guidelines do not recommend its initiation during pregnancy. Dedicated prospective trials (IMPAACT 2040, IMPAACT 2050) are ongoing to provide the pharmacokinetic, safety and neonatal outcome data required to inform evidence-based clinical guidance.