A multicentre real-life prospective cohort study on effectiveness, durability and safety of long-acting injectable cabotegravir and rilpivirine in northern Italy: the LONGITUDE study

Abstract

Objectives: We herein present a prospective multicentre experience of long-acting injectable (LAI) cabotegravir/rilpivirine from 11 different HIV clinics in northern Italy, focusing on the regimen's effectiveness, durability and safety in a real-life setting.

Methods: We included all people who received at least one dose of LAI cabotegravir/rilpivirine, recording clinical data, and assessing factors associated with treatment discontinuation (TD) for any cause. Kaplan-Meier curves were used to estimate the probability of TD, and Cox regression models identified significant predictors of TD. A sub-analysis was conducted focusing on TD due to virological failure (VF, defined as two consecutive HIV-RNA values >200 copies/mL or a single value over 200 copies/mL leading to treatment withdrawal).

Results: We included 483 participants (81.6% males) with a median age of 49 (IQR: 40-58) years. In 74.1% of participants, the LA regimen was started by choice, with 51.8% coming from a dual oral antiretroviral regimen. During a median follow-up time of 22 (IQR: 13-26) months, 54 (11.1%) participants had TD (incidence = 0.627 per 100 person-months of follow-up), mostly due to side effects (31, 6.4%) but with 7 (1.4%) due to VF [with people reporting major integrase strand transfer inhibitor (INSTI) and NNRTI resistance mutations in 71.4% cases]. When multivariable analysis was performed, age, years with HIV, CD4/CD8 ratio and BMI were significantly associated with TD. Also, we detected that the number of previous antiretroviral regimens was significantly associated with VF.

Conclusions: Despite the overall effectiveness, TD was observed in a specific subset of people, primarily due to side effects, with a smaller proportion experiencing VF. Factors associated with both TD and VF underscore the importance of personalized selection to optimize LAI cabotegravir/rilpivirine outcomes and to improve regimen persistence.