Immune Trajectories After Switch to Long-Acting Cabotegravir Plus Rilpivirine in the RELATIVITY Cohort

Immune and virological trajectories after switching to long-acting cabotegravir plus rilpivirine (CAB+RPV LA) remain incompletely characterized in routine care settings.

We analyzed virologically suppressed adults switching to CAB+RPV LA in the Spanish multicenter RELATIVITY cohort. Paired CD4+, CD8+, and CD4/CD8 measurements were assessed at approximately 12 and 24 months and at the last available immune assessment. Analyses used a 1.0 ratio threshold and incorporated longitudinal HIV-1 RNA, recorded geographic origin, pre-switch suppression duration, and immediate pre-switch antiretroviral therapy.

Among 3349 participants, the last paired-ratio assessment (n = 2929) occurred at a median of 22 months (IQR, 16-27). Median changes were -7 cells/mm³ (IQR, -138 to +117; n = 2992) for CD4+ T-cell count, -60 cells/mm³ (IQR, -214 to +75; n = 2941; P < .001) for CD8+ T-cell count, and +0.07 (IQR, -0.05 to +0.20; n = 2929; P < .001) for the CD4/CD8 ratio. Baseline CD4/CD8 <1.0 was independently associated with greater ratio increase (adjusted beta, +0.060; 95% CI, +.030 to +.090; P < .001). Longer pre-switch suppression and any post-switch HIV-1 RNA ≥50 copies/mL were associated with smaller ratio increases. Adjudicated virological failure occurred in 28/3349 (0.8%). Findings persisted among participants with all recorded post-switch HIV-1 RNA values <50 copies/mL and after excluding protocol-defined virological failure.

During effective CAB+RPV LA maintenance, CD4+ T-cell counts showed no meaningful change, while a modest decline in CD8+ T-cell counts was accompanied by a small CD4/CD8 ratio increase. These descriptive changes are compatible with continued immune evolution during sustained suppression and do not establish a CAB+RPV-specific effect or justify additional routine T-cell-subset monitoring.