Long-term real-world outcomes of long-acting cabotegravir plus rilpivirine in people with HIV in Japan: implications for clinical practice

Abstract Background To evaluate the implications of long-acting injectable (LAI) cabotegravir plus rilpivirine (CAB + RPV) for HIV treatment management in routine clinical care in Japan, focusing on injection adherence, transient and low-level viremia, and longitudinal changes in lymphocyte counts and renal biomarkers. Methods We conducted a retrospective cohort study of people with HIV (PWH) who received CAB + RPV at a tertiary HIV center in Japan between July 2022 and August 2026. Longitudinal changes in injection adherence, low-level viremia, lymphocyte counts, and renal biomarkers were evaluated. Results Among 108 PWH, the median follow-up was 45 months (IQR, 30–47). During follow-up, 12 participants (11.1%) discontinued CAB + RPV. Of 2,041 scheduled visits, 95.8% were within the recommended dosing window, 2.94% were early, and 1.22% were late. Generalized estimating equation (GEE) logistic regression analysis showed no significant association between injection visit number and late administration. Among 2,008 HIV RNA measurements, 97.8% were < 50 copies/mL, including 77.0% that were target not detected. Three measurements of ≥ 200 copies/mL occurred in one participant, without consecutive elevations or virological failure. GEE analysis showed no significant change in HIV RNA ≥ 50 copies/mL over time. Linear mixed-effects model analysis showed stable CD4 counts, decreased CD8 counts, and an increased CD4/CD8 ratio. Serum creatinine decreased initially after switching to CAB + RPV, as reflected in the Month 5 comparison, while cystatin C remained unchanged. Conclusions In this real-world cohort, CAB + RPV use was characterized by high injection adherence, sustained virological control, and no adverse longitudinal changes in the measured immunological and renal biomarkers over up to four years.