Journal Article

SC28 Adverse event development in people with HIV on long-acting Cabotegravir + rilpivirine: timing and clinical insights

Lagi, F, Pontali, E, Franzetti, M, Cenderello, G, Menzaghi, B, Bonfanti, P, Salomoni, E, A Di Biagio, Taramasso, L, Orofino, G, Falasca, K, Rusconi, S, Cologgi, G, Bargiacchi, O, Pellicanò, G F, Sarchi, E, Ferrara, S, Madeddu, G, Bini, T, Martini, S, Calza, L, Pusterla, L, Carleo, MA, Ricci, E

2025

Overview

BackgroundLong-acting (LA) injectable cabotegravir (CAB) and rilpivirine (RPV) is a well-established and tolerated option for antiretroviral treatment (ART) in eligible people with HIV (PWH). This study aims to describe adverse events (AEs) reported in a multicentric, prospective cohort, assessing their severity and the timing of occurrence. Additionally, it explores the characteristics of PWH who experienced these reactions.Materials and MethodsThis observational, prospective multicentric study included PWH who started LA CAB/RPV regimen and developed an AE between July 2022 and February 2025. AEs were defined, according to the study protocol, as any harmful and unintended effect, graded using the DAIDS Adverse Event Grading, resulting from the use of the LA regimen. Data were described using mean ± standard deviation (SD) for normally distributed continuous variables, median and interquartile range (IQR) for not normally distributed continuous variables and percentage for categorical and ordinal variables.ResultsA total of 667 PWH who initiated the LA treatment were included, 512 were male (76.8%) and had a median age of 49 (IQR 40–58). Most were in CDC stage A (379/667, 56.8%) and had a mean prior ART duration of 12.0 years (SD 7.6). At baseline, 654/667 (98.0%) had undetectable viral load, with a median CD4+ T count of 780 cells/mm³ (IQR 568–1015). Additionally, 352/667 (52.8%) were on at least one concurrent treatment.In our cohort, 42 (6.3%) PWH developed ≥1 AE. In 7/42 (16.7%), AEs were difficult to correlate with the LA treatment or were not assessable.PWH with AEs had a median age of 54 years (IQR 47–61) and were mostly males (32/42, 76.2%); 26/42 (61.9%) were concurrently receiving at least one other pharmacological treatment. Most PWH staged CDC class A (21/42, 50.0%), with mean prior ART duration of 14.0 years (SD 9.1) and a baseline CD4+ T count of 750 cells/mm³ (IQR 497–1074). Baseline CD4+ T count was not significantly different between PWH with and without AEs (p=0.57).Prior to the initiation of LA regimen, 31/42 PWH (73.8%) received an oral ART with INSTIs, and 18/42 (42.9%) with NNRTIs. The median follow-up period for PWH with AE was 3 months (IQR 2–6); AEs mainly occurred within the first 66 days (IQR 28–176) after the first injection. Thirty-seven/42 (88%) PWH discontinued due to AEs. The most prevalent AEs were injection site reaction (13/42, 30.9%) and lower limb pain (7/42, 16.7%), followed by fever (6/42, 14.3%) and neurological symptoms (4, 9.5%). Nine PWH (21.4%) developed more than one AE.In regard to severity, only two AEs related to the LA regimen (34/42) were grade 4 and ten grade 3; 5/42 had no grading, while 18/34 were graded 1 and 2.Abstract SC28 Figure 1Development of adverse events over the course of treatment, with time zero defined as the start of treatment. Abbreviation: PWH - People with HIV[Figure omitted. See PDF]ConclusionsReal-life data confirm that LA CAB/RPV is well-tolerated, with most AEs occurring within the first months of treatment (figure 1). AE rates were lower than in registration trials, especially for injection site reaction, though more PWH discontinued LA due to AEs.

• Publisher: BMJ Publishing Group LTD
• Subject: Antiretroviral drugs / HIV / Human immunodeficiency virus