Background
The advent of long-acting (LA) injectable ART has transformed the conceptualization of ART. However, there is a need for Real World Data on the impact of this novel approach on peripheral inflammation. The aim of this study was to investigate the dynamic changes in monocyte/macrophage subsets and their soluble activation markers in PLWH switching to LA injectable ART (CAB/RPV).
Methods
The present study investigated the percentages of peripheral blood monocyte/macrophage and dendritic cell subsets (HLA-DR, CD14, CD16, CD11c, CD123) in samples obtained from PLWH before CAB/RPV (T0) and after six (T6) and twelve months (T12) by flow cytometry. Moreover, a longitudinal evaluation of monocyte/macrophage activation markers (sCD14 and sCD163) was conducted. Subsequently, each time point was compared to a control group (healthy donors, HDs).
Results
A total of 30 aviremic PLWH switching to CAB/RPV, and 32 HDs were enrolled. All the enrolled PLWH were ART-experienced (12 dual/18 no dual) and 93.3% had a viral load of <50 copies/mL prior to initiating LA ART. At T12, no virological failure was observed. In comparison to HDs, PLWH exhibited higher percentages of intermediate monocytes (p=0.0037), non-classical monocytes (p<0.0001), M-DC8 (p=0.0007) and elevated plasma levels of sCD14 (p<0.0001) and sCD163 (p<0.0001) at each time point. The stratification of PLWH according to previous ART revealed no differences in the percentages of monocyte/macrophage subsets or in the plasma levels of sCD14 and sCD163 between dual and no dual therapy.
Overall, at both T6 and T12, a significant reduction in the percentage of non-classical monocytes compared to T0 was observed (p=0.0054 and p=0.0017, respectively). No significant differences were observed in the percentages of classical monocytes, intermediate monocytes, M-DC8, pDCs and mDCs. Furthermore, a reduction in sCD14 plasma levels was observed at both T6 and T12 in comparison to T0 (p=0.0006 and p=0.0237, respectively). No differences in sCD163 plasma levels were observed (see Table).
Conclusions
The significant reduction in inflammation and peripheral immune activation of the monocyte compartment observed after 12 months of LA injectable CAB/RPV underlines that the potential contribution of these cells to the viral reservoir and persistence may vary with therapy. The constant drug concentrations provided by CAB/RPV injections appear to be sufficient for sustained virological suppression and may affect the monocyte/macrophage compartment in PLWH.
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