CROI 2025: Key Updates on ViiV Healthcare’s Cabenuva and Apretude

The 2025 Conference on Retroviruses and Opportunistic Infections (CROI), which was held March 9 through March 12 in San Francisco, California, showcased updates in 2 key HIV treatment and prevention methods from ViiV Healthcare: cabotegravir/rilpivirine long-acting (CAB/RPV LA, Cabenuva) and cabotegravir LA (CAB LA, Apretude). The abstracts and presentations that were showcased at this meeting involved real-world implementation of data to highlight the effectiveness of these treatments.¹

Cabenuva

Image credit: jarun011 | stock.adobe.com

In January 2021, Cabenuva was approved as a complete regimen designed to replace the antiretroviral (ART) regimen in adults with HIV-1 infection who were considered virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable ART regimen and without a history of treatment failure and no known or suspected resistance to either cabotegravir or rilpivirine.² The treatment is indicated for adults and adolescents who are 12 years and older and weigh at least 35 kg.³

Initiation doses are 600-mg/900-mg injections, and continuation doses are 400-mg/600-mg injections that are administered a month following the initiation dose. The treatment’s initial approval was based on data from 2 randomized, multicenter, active-controlled, parallel-arm, open-label, non-inferiority phase 3 trials, FLAIR (Trial 201584; NCT02938520) and ATLAS (Trial 201585; NCT02951052).²

Key Updates on Cabenuva Presented at CROI 2025

Outcomes on Cabotegravir + Rilpivirine in Suppressed People with HIV (PWH) in TRIO Health US Cohort

An update from the Trio Health cohort, which followed 928 virologically suppressed individuals who initiated Cabenuva in real-world settings in the US, shows that the median (IQR) follow-up time following the first injection was about 12 months (range: 5-19), and 89% of injections (n = 6176 of 6934) were administered without delay (< 7 days following the target dosing date). Additionally, approximately 95% of individuals on Cabenuva had maintained viral suppression (last viral load [VL] <50 c/mL), and about 1.6% (n = 15) experienced confirmed virologic failure (CVF).

Real-World Data From OPERA Show High Effectiveness of CAB + RPV LA in Broad Populations

The first of 2 OPERA analyses evaluated the long-term effectiveness (over 2 years) in diverse virologically suppressed individuals on Cabenuva, approximately 42% and 30% of whom are Black and Hispanic, respectively. Among a total of 2,485 US individuals who switched to Cabenuva, 95% had maintained virological suppression (<50c/ml at last VL), with a median follow-up time of about 11 months (IQR: 6-18). Additionally, approximately 1% (n = 21) experienced confirmed virologic failure (CVF) after a median of 7 months. These outcomes were consistent over time through 24 months and across body mass index categories (<30 kg/m², ≥30 kg/m²).

A second analysis enrolled a diverse group of 381 virologically suppressed women with HIV. At a median follow-up of 12 months (IQR: 7-19), 94% had maintained suppression at their last VL, and CVF was 1.3% or less (n ≤ 5).

Randomized Trial of Cabotegravir and Rilpivirine Long-Acting in Africa (CARES): Week 96 Results

The aim of the randomized CARES trial was to demonstrate the sustained virologic response and safety of switching virologically suppressed adults to Cabenuva every 8 weeks compared with the continuation of an oral standard of care in a sub-Saharan African population. This phase 3b trial determined that, in this population, about 97% had VL suppression (< 50 copies/mL), and only 1.6% (n = 4) had CVF at 96 weeks. Three patients had resuppressed after switching to other PrEP methods. Participants who switched to Cabenuva had also reported a greater increase in satisfaction score.⁴

Further, Cabenuva was also shown to have a positive safety profile and was well-tolerated among participants. Only 2% had severe AEs (grade 3 or higher) that were related to the study medication. Injection site reactions were mostly grades 1 and 2 in severity, and only 1 patient discontinued the study because of this AE.⁴

Apretude

Approved in December 2021, Apretude is indicated for use in at-risk adults and adolescents who weigh at least 35 kg for PrEP to reduce the risk of sexually-acquired HIV. It is given first as 2 initiation injections that are administered 1 month apart, and then every 2 months thereafter. Patients are able to initiate treatment with Apretude or take oral cabotegravir for 4 weeks to assess how well they tolerate the drug. The approval was based on 2 randomized, double-blind trials that compared Apretude to Truvada (emtricitabine/tenofovir disoproxil fumarate; Gilead Sciences, Inc). These trials enrolled cisgender men, transgender women who have sex with men, and cisgender women.⁴

Key Updates on Apretude Presented at CROI 2025

PILLAR 12-Month Clinical Results: Zero HIV Acquisitions and High Persistence With CAB LA for PrEP

New 12-month findings from the phase 4 implementation trial, PILLAR (NCT05374525), demonstrate effectiveness, diagnostic testing, persistence, safety, and tolerability of Apretude in a total of 201 participants. PILLAR assessed the integration of Apretude for pre-exposure prophylaxis (PrEP) in patients who were transgender men or men who have sex with men (MSM) from 17 US clinics. Among these participants, approximately 26% and 38% were Black and Hispanic or Latino, respectively.³

The findings indicated there were no cases of HIV acquisition throughout the 12-month duration, with about 85% (n = 171) of participants remaining persistent (defined as the time that an individual continued to receive their injections) at 6 months, and 72% (n = 142) at 12 months. Notably, 5 patients were excluded because they completed the study post-data cutoff, and 5 more missed an injection and had to receive either an alternative PrEP or oral Apretude.³

Adverse events (AEs) related to treatment were uncommon, according to the investigators, with injection site pain being the most frequently reported (3%; n = 6). Additionally, 5% (n = 11) of patients had AEs that led to study discontinuation. Regardless, these findings support the continued use of Apretude as a PrEP method.³

ImPrEP CAB Brazil Implementation Study Data Shows Significantly Improved PrEP Coverage and Protection With CAB LA

Findings from the ImPrEP CAB Brazil study (the Choice Cohort) show that Apretude significantly improved PrEP coverage and HIV prevention for key youth populations, such as MSM, non-binary, and transgender people aged 18 to 30 years. A total of 1447 participants were enrolled in the study and given the option of Apretude or other oral PrEP. Most of the population (83%; n = 1200) chose Apretude over the oral option, and among these patients, there were no HIV acquisitions reported over 798.4 person-years in the Choice Cohort.³

Additionally, as a comparison group, 2263 people of a similar demographic initiated oral PrEP. In this group, there were 8 HIV acquisitions over 408.52 person-years reported (incidence rate: 1.96 [95% CI 0.98-3.92] per 100 person-years). The proportion of individuals covered by PrEP during follow-up was highest in the Apretude group (96.2%; 221,273/229,951 days), followed by the oral PrEP group within the Choice Cohort (64.1%; 32,272/50,310 days). The lowest rate was observed in the comparison group (47.4%, 191,765/404,781 days).³

“Our long-acting injectable portfolio [was] showcased at CROI 2025 with data on real-world outcomes, demonstrating the impact our industry-leading portfolio is having today,” Kimberly Smith, MD, MPH, head of research & development at ViiV Healthcare, said in a news release. “These assets have the potential to increase dosing intervals beyond what's currently available, aiming to deliver what the community of people living with HIV tells us they want and need.”¹

REFERENCES

1. ViiV Healthcare. ViiV Healthcare continues to deliver long-acting injectable HIV innovation with late-breaking data and real-world insights across pipeline and portfolio at CROI 2025. News release. March 9, 2025. Accessed March 14, 2025. https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/march/deliver-long-acting-injectable-hiv-innovation/

2. US Food & Drug Administration. FDA Approves Cabenuva and Vocabria for the Treatment of HIV-1 Infection. News release. January 27, 2021. Accessed March 14, 2025. https://www.fda.gov/drugs/human-immunodeficiency-virus-hiv/fda-approves-cabenuva-and-vocabria-treatment-hiv-1-infection

3. ViiV Healthcare. ViiV Healthcare announces new implementation study data showing zero cases of HIV with Apretude, the only long-acting injectable approved for HIV PrEP. News release. March 12, 2025. Accessed March 14, 2025. https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/march/new-implementation-study-data/

4. Kityo C, et al. Randomized Trial of Cabotegravir and Rilpivirine Long-Acting in Africa (CARES): Week 96 Results. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2025), 9-12 March, San Francisco, CA

5. US Food & Drug Administration. FDA Approves First Injectable Treatment for HIV Pre-Exposure Prevention. News release. December 20, 2021. Accessed March 14, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-injectable-treatment-hiv-pre-exposure-prevention