Long-Acting Injectable Cabotegravir Effective in Both ART, PrEP

Cabotegravir (Vocabria; ViiV Healthcare) was found to have multiple uses in studies presented at the Conference on Retroviruses and Opportunistic Infections 2025, held in San Francisco, California, from March 9 to March 12, 2025. Cabotegravir was effective as a means of pre-exposure prophylaxis (PrEP) as a monotherapy, and its use also extended as an antiretroviral therapy (ART) when taken in combination with rilpivirine (Edurant; ViiV Healthcare).

Long-Acting Cabotegravir as Long-Term PrEP

The PILLAR trial1 is a phase 4 trial that aimed to assess long-acting cabotegravir in 17 clinics that served men who have sex with men (MSM) and transgender men. Incidence of HIV, duration of receiving injections, diagnostic testing for HIV, and safety were all assessed in the participating individuals.

There were 201 participants who enrolled for the study between May 2022 and August 2023, of which 6% were transgender men. The median (IQR) age was 35 (29-44) years; 26% of the participants were Black and 38% were Hispanic. Oral PrEP had been taken by 78% of the participants before they began receiving the long-acting injection of cabotegravir.

Long-acting cabotegravir can be utilized as both PrEP and ART effectively | Image credit: jarun011 - stock.adobe.com

No new cases of HIV were reported by the participants after 12 months, with 72% of the participants persisting with injections through all 12 months. Sexually transmitted infections were reported in 27 participants, with gonorrhea (14), chlamydia (12), and syphilis (7) reported by the participants. Completion of all injections was achieved by 70% of the participants, though 2% of the participants missed 1 dose and received an alternate oral cabotegravir or PrEP to make up for the medication. Injection site pain (3%) was the most reported adverse event related to the medication. Only 5% of the participants discontinued due to the adverse events.

The researchers concluded that long-acting cabotegravir was an effective method of PrEP, with no new cases of HIV through 12 months, offering an alternative method of PrEP that would allow for less frequent intake of medication.

"PILLAR reinforced safety and effectiveness of cabotegravir across diverse populations and clinical settings, underscoring the importance of real-world PrEP studies to build on robust clinical trials," said Taimur Khan, MD, MPH, associate medical research director at The Fenway Institute and coauthor of the study.

Combination Therapy With Cabotegravir Effective as ART

Another study presented at the conference focused on using cabotegravir in combination with rilpivirine as an alternative form of ART, utilizing the Trio cohort to assess the efficacy in a real-world setting.2 This treatment also utilized the long-acting form of the medication, but participants were all patients living with HIV who had previously used ART and had undetectable viral loads of less than 50 copies/mL.

All adults in the Trio Health Cohort who had an undetectable viral load and received 1 or more injections of cabotegravir plus rilpivirine between February 2021 and March 2024 were included in the study. All participants had follow-ups after 6, 12, and 24 months. Any injections that happened more than 7 days after the target date were considered delayed injections. ART resistance was analyzed when the data were available.

There were 1198 participants included in the study and had a median follow-up of 12 (5-9) months after the first injection. There were 944 participants who continued using cabotegravir plus rilpivirine after the end of the follow-up period. A total of 69% of participants had no delayed injections. A last viral load of less than 50 copies/mL was observed in 95% of the participants who had 1 or more follow-up viral loads measured. Virologic failure was reported in 1.6% of the participants.

A total of 27% of the participants with virologic failure had injection delays compared with 31% of all participants. There were 5 participants with virologic failure who had genotype data available, of whom 3 had resistance to rilpivirine.

"I think what this study shows is that, in clinical practice, the use of cabotegravir/rilpivirine performs very similarly to the clinical trials, which is reassuring," Paul E. Sax, MD, clinical director of the division of infectious diseases at Brigham and Women's Hospital and coauthor of the study, said in a statement to The American Journal of Managed Care®. "The chaos of real-patient data still works out okay."

The researchers concluded that people living with HIV had high rates of viral suppression when using cabotegravir plus rilpivirine, and resistance to cabotegravir with virologic failure was rare. Both studies demonstrate the versatility of cabotegravir as both a means of preventing and treating HIV in patients. The long-acting nature of the treatment also encourages persistence through the decreased number of required doses.

References

1. Khan T. PILLAR Month 12 Clinical Results: Zero HIV Acquisition and High Persistence With CAB LA for PrEP. Presented at Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 196
2. Sax PE, Frick A, Radtchenko J, et al. Outcomes on cabotegravir + rilpivirine in suppressed people with HIV (PWH) in TRIO Health US cohort. Presented at Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 675