Discussion
inflammation, atherosclerosis, HIV infection, non-AIDS
HIV INFECTION, INFLAMMATION, DYSFUNCTION, EVENTS, ATHEROSCLEROSIS, PERSISTENT INFLAMMATION, ENDOTHELIAL DYSFUNCTION
Our randomized study shows no evidence for a difference in absolute CD4+ and CD8+ T-cell counts and in CD4/CD8 ratio trajectories over 12 months of follow-up by study arm (DTG/3TC However, importantly, our data provide additional insights concerning immunological changes after switching from 3DR treatment to DTG/3TC or B/F/TAF. First, the increase in CD4+ and to a lesser extent in CD8+ activated T cells, coupled with an increase in transitional memory and terminally differentiated cells, especially at 6 months after switching to DTG/3TC, but not after switching to B/F/TAF, could indicate an effect of DTG/3TC, which goes beyond reaching an undetectable plasma viral load. Second, in order to synthesize soluble or plasma membrane molecules that provide signals to the cells of interest, monocytes have to receive stimulatory signals that activate them. The analysis of the changes in monocyte subpopulations reveals a significant difference by arm at 6 months in non-classical monocytes, including intermediate cells that have inflammatory properties.The balance between monocyte subsets is disrupted after HIV infection, and the number and function of these cells are not completely restored even after long-term ART (As for T-cell activation, inflammation in response to a phenomenon could be only transient since the immune system tries to reach a new balance, which could explain, at least in part, the changes in monocyte populations that were observed at time 6, but to a less extent at time 12 in the DTG/3TC group. Thus, during HIV infection as well as in its treatment, proportions of monocyte subgroups (classical, intermediate, and non-classical) can provide information regarding the level of residual immune dysfunction and associated risk of serious non-AIDS events (Concerning cardiovascular risk, persistent inflammation and immune activation have been hypothesized to promote atherosclerosis in PLWH (Concerning IL-6 trajectories, our results are consistent with those of a recent meta-analysis of all published data (including both real-world and randomized studies) showing inconclusive results regarding the level of inflammation after switching to DTG/3TC compared to those seen with 3DRs (In a real-world study evaluating inflammatory biomarkers, median sCD14 significantly decreased 48 weeks post-switch to DTG/3TC, while other biomarkers remained stable (Our study has several limitations. First of all, as in most small trials, despite randomization (However, this analysis has several strengths. First of all, our analysis confirms that in the rigorous context of a randomized comparison in PLWH with ≤50 copies/mL, after 1 year of therapy, there is little evidence for a difference in immune response when comparing DTG/3TC with B/F/TAF. In addition to randomization, there is the fact that although this study was open-label, all laboratory analyses were conducted without knowing the treatment received by the patients. Moreover, our data could provide a glimpse of what is happening in the lymphoid tissues. Indeed, we observed changes in different blood cell populations that play a key role in triggering or maintaining the immune response, including inflammation. There are two main aspects to consider about this. First, the number of cells in blood represents just a small proportion (approximately 2%) of those belonging to innate or acquired immunity. Thus, even a minimal change in this compartment could be a signal for a much larger change at the level of a number of immune tissues.In conclusion, our study showed no evidence for a difference in absolute CD4 and CD8 T-cell counts and CD4/CD8 ratio trajectories over 12 months between DTG/3TC and B/F/TAF after the switch. However, the switch to DTG/3TC was associated after 6 months with statistically higher levels both in CD4+ and CD8+ T lymphocytes with markers related to terminal differentiation and exhaustion and in non-classical monocytes, a population of cells that has been recently associated with endothelial dysfunction. Further studies investigating a wider range of dual antiretroviral combinations, longer follow-up, and the power to detect differences in harder clinical outcomes are needed to confirm the clinical impact of our findings.