Key Takeaways
- LATITUDE confirms Cabenuva halves regimen failure vs. oral therapy in adherence-challenged HIV patients.
- First randomized superiority evidence expands long-acting options for high-risk populations.
- Comparable safety profile, primarily injection site reactions, supports broad applicability.
- Paves way for studies like CROWN in unsuppressed patients, advancing HIV control goals
Written By: Pavan Kumar Chikkula PharmD
Reviewed By: Pharmacally Editorial Team
ViiV Healthcare announced final 48-week results from the phase III LATITUDE trial, showing Cabenuva (cabotegravir + rilpivirine), a long-acting injectable HIV treatment, outperformed daily oral therapy in maintaining viral suppression among patients with adherence issues. Published in the New England Journal of Medicine, these findings followed a 2024 Data Monitoring Board recommendation to halt randomization due to early efficacy signals, allowing eligible participants to switch to the injectable regimen.
Kimberly Smith, MD, MPH, ViiV’s Head of Research & Development, noted LATITUDE as the first randomized evidence of Cabenuva’s superiority over oral therapy in this population, potentially expanding access for those struggling with adherence and advancing HIV epidemic control goals.
LATITUDE Trial
The LATITUDE study (NCT03635788) enrolled 453 adults facing daily oral ART challenges or disengaged from care, randomized 306 virally suppressed participants to Cabenuva every four weeks (n=152) or continued oral therapy (n=154). Median age was 40 years, with 63% Black/African American, 29% female, 17% Hispanic, and 14% reporting injection drug use history; all received adherence support like incentives pre-randomization. This open-label, NIAID-funded trial via ACTG targeted a high-risk group, confirming viral suppression eligibility before comparing regimens.
Key Efficacy Results
Regimen failure, virologic failure (VF) or discontinuation was nearly halved with Cabenuva at 22.8% (29/152) versus 41.2% (55/154) for oral therapy, achieving the primary endpoint. VF events were low: 3% (5/152) first in Cabenuva arm (19% total failure) versus 21% (32/154) first in oral arm (36% total). Additional metrics showed superiority: VF incidence 6.8% (6 events) for Cabenuva vs. 28.2% (34) for oral (difference -21.4%, 98.4% CI -33.5% to -9.3%); treatment-related failure 8.9% vs. 28.1% (-19.2%).
Endpoint (48 Weeks) | Cabenuva (n=152) | Oral Therapy (n=154) | Difference (98.4% CI) |
VF (events) | 6.8% (6) | 28.2% (34) | -21.4% (-33.5%, -9.3%) |
Treatment-Related Failure* (events) | 8.9% (9) | 28.1% (34) | -19.2% (-31.6%, -6.9%) |
Permanent Discontinuation (events) | 19.8% (26) | 28.2% (37) | -8.4% (-21.3%, 4.5%) |
Safety and Resistance Profile
Adverse event (AE) rates were comparable across arms, with injection site reactions (ISRs) most common for Cabenuva two discontinuations occurred. Four confirmed VFs total (two per arm) showed new resistance mutations, including two integrase inhibitor RAMs in Cabenuva cases, highlighting similar resistance risk despite lower VF incidence.
ViiV Healthcare has stated that, building on LATITUDE, the ongoing CROWN study (NCT06694805) tests Cabenuva in unsuppressed patients with adherence issues, bypassing the suppression phase used in LATITUDE.
Cabenuva Mechanism
Cabenuva, a complete regimen for virologically suppressed HIV-1 patients (≥12 years, ≥35 kg) without cabotegravir or rilpivirine resistance, pairs ViiV’s integrase strand transfer inhibitor (INSTI) cabotegravir which blocks viral DNA integration into T-cells with Janssen’s non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, inhibiting reverse transcriptase.
Trial Sponsors
LATITUDE was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), executed by the AIDS Clinical Trials Group (ACTG), with support from the National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), ViiV Healthcare, and Johnson & Johnson.
ACTG, the largest HIV trials network since 1987, advances treatments across 65 global sites. Full prescribing information is available via ViiV.
References
ViiV healthcare’s long-acting cabenuva (cabotegravir + rilpivirine) for HIV demonstrates superior efficacy compared to daily oral therapy for people with adherence challenges; results published in NEJM, 18 February 2026, https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2026/february/daily-oral-therapy-for-people-with-adherence-challenges/
Aadia I et al. Cabotegravir plus Rilpivirine for Persons with HIV and Adherence Challenges. New England Journal of Medicine. Published February 18, 2026, https://www.nejm.org/doi/full/10.1056/NEJMoa2508228
The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE, ClinicalTrials.gov ID NCT03635788, Study Details | NCT03635788 | The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE | ClinicalTrials.gov
A Study to Evaluate the Effectiveness of Long-acting (LA) Cabotegravir (CAB) + Rilpivirine (RPV) LA When Given to Participants with Detectable HIV-1 (CROWN), ClinicalTrials.gov ID NCT06694805, https://clinicaltrials.gov/study/NCT06694805