Real-World Safety and Effectiveness of Cabotegravir in People Living with HIV: Interim Report of a Post-marketing Surveillance in Japan

Cabotegravir (CAB) is an integrase strand transfer inhibitor and the first long-acting injectable antiretroviral agent for human immunodeficiency virus (HIV), administered with rilpivirine. Because approval in Japan relied largely on overseas and international collaborative trials, domestic real-world evidence remains limited. This study evaluated the real-world safety and effectiveness of CAB in people living with HIV (PLHIV) in Japan. This interim analysis (June 27, 2022 and June 17, 2025) was part of an ongoing post-marketing surveillance of Japanese PLHIV treated with CAB at institutions participating in the HIV-related Drugs Cooperative Survey. Safety was assessed by the incidence of adverse drug reactions (ADRs). Associations between ADR incidence and background characteristics were examined using Fisher’s exact and χ2 tests without multiplicity adjustment. Effectiveness was evaluated using virologic suppression assessed by log-transformed HIV RNA copies/mL and peripheral CD4+ cell counts. A total of 121 and 117 participants were included in the safety and efficacy analysis sets, respectively; most were aged over 20 years, and over 96% were male participants. Overall, 76 ADRs were reported in 45 participants (37.19%). The most frequent ADRs were injection site pain and musculoskeletal pain (12.40% each). Four serious ADRs that were not explicitly deemed unrelated to CAB by the reporting physicians occurred in 4 participants: hepatitis B reactivation, monkeypox, syphilis, and type 2 diabetes mellitus. Stratification analyses by participant characteristics revealed high ADR incidences among participants aged ≥ 30 to < 40 years (p = 0.038), without allergy (p = 0.016), and with comorbidities (p = 0.045). HIV RNA copies remained suppressed and CD4+ cell counts were maintained at levels comparable to treatment initiation throughout follow-up. This interim analysis indicates that CAB therapy is safe, with no new safety signals, and effective, as demonstrated by sustained virological suppression and stable CD4+ cell counts. These findings are consistent with outcomes reported in overseas and international collaborative clinical studies. Taking multiple oral medications every day can be challenging for people living with human immunodeficiency virus (PLHIV). Cabotegravir, co-administered with rilpivirine, is the first long-acting injectable HIV treatment that can be given once monthly or every 2 months. Its approval in Japan was primarily based on overseas and international collaborative studies, and real-world clinical evidence in Japan has been limited. To address this gap, a post-marketing surveillance has been conducted to confirm the safety and effectiveness of cabotegravir in Japanese PLHIV. This was a 3-year interim analysis of post-marketing surveillance including 121 participants at 10 institutions in Japan who were virologically suppressed for over 6 months before switching to cabotegravir. During follow-up, 45 participants experienced 76 adverse drug reactions (37.19%) that included injection site pain and musculoskeletal pain (12.40% each), and oral herpes, high cholesterol, thickened or hardened injection site, fever, and decreased white blood cell counts (2.48% each). These findings were consistent with those reported in previous clinical studies. Higher adverse drug reaction rates were observed among participants aged ≥ 30 to < 40 years, those without allergy, and those with other medical conditions. Most adverse drug reactions considered related to cabotegravir occurred within 180 days after treatment initiation. Throughout the follow-up period, HIV RNA copies remained suppressed and CD4+ cell counts were maintained at levels similar to those at treatment initiation. Overall, these results confirm the real-world safety and effectiveness of cabotegravir in Japan.