Abstract
BACKGROUND: Despite effective ART, HIV infection remains a chronic condition, characterized by a persistent inflammation and immune activation. Currently, there is limited evidence comparing the role of different therapies in this context. Long-acting (LA) formulations may better bioavailability and modulate the immunoinflammatory state associated with the disease. For this reason, we provide an analysis of the dynamic changes in the lymphoid immune activation and senescence markers in PWH switching to LA injectable ART (CAB/RPV), compared to a PWH on oral ART. METHODS: An evaluation of immune activation (CD38+HLA−DR+) and T-cell senescence (CD28−CD57+) was performed before CAB/RPV (T0), at 4 (T4), 28 (T28), 48 (T48) and after 72(T72) weeks of follow-up. Each time point was compared with the control group (CG) of PWH on daily oral ART at both T0 and T48. RESULTS: A total of 37 aviremic PLWH switching to CAB/RPV LA and 9 PLWH on daily oral ART were enrolled. At T72 all PWH had VL below 50 copies/mL. Overall, in PWH switching to CAB/RPV LA, a non-significant increase in CD4 is observed over time with a higher percentage of CD4 than CG, while the percentage of CD8 remains stable. In PWH switching to CAB/RPV LA, the CD4 immune-activation status declines, with a significant reduction at T48 and T72 compared to T0(P = 0.0350 and P < 0.0016, respectively), while the CD8 immune-activation remains stable over-time. The cross-sectional evaluation of CD4(CD38+HLA−DR+) showed a lower percentage in PWH switching to CAB/RPV LA compared to GC at T48(P = 0.0079). Concerning the immunosenescent T-cell phenotype, an overall reduction over-time is observed in both CD4 and CD8 compartments, with significantly lower CD8(CD28−CD57+) in PWH switching to CAB/RPV LA compared to CG at T48 (P = 0.0044). CONCLUSION: In summary, CAB/RPV LA is not only effective in controlling viral load, but also in maintaining a healthy and stable immune profile. Specifically, it appears to offer several benefits in possibly reducing immune activation and slowing immune senescence. For this reason, in our opinion, future studies should aim to explore the long-term effects of CAB/RPV LA on immune activation and senescence in view of optimizing treatment strategies and improving the prognosis of PWH. [Figure: see text]