IL-18 and MIG increase one year after transition to dolutegravir-based dual therapy despite sustained viral suppression

Introduction Modern antiretroviral treatment allowed a significant improvement in the life expectancy of people with HIV (PWH), exhibiting robust and sustained efficacy with scarce toxicities, both in two-drug regimens (2DRs) and three-drug regimens (3DRs). However, a proinflammatory condition is observed even in virologically suppressed PWH. The aim of this study is to assess prospectively the dynamics of various cytokines in PWH who transition from a 3DR to a 2DR. Methods A prospective cohort study including 35 virologically suppressed PWH who switched from a 3DR to a dolutegravir-based 2DR was conducted. Plasma concentrations of IL-6, IL-18, IP-10, MIG and IL-18BP were quantified using a multiplex bead-based immunoassay (MILLIPLEX ® ) in samples collected at baseline month 3, month 6 and month 12; an exploratory extension analysis was performed in a subset of 6 participants up to 24 months. Results Between June/2021 and December/2022, 35 subjects were recruited, of whom mostly were men ( n = 25, 71.4%), born in Spain ( n = 27, 62.8%), with a median time receiving ART of 10.7 years. Throughout the study period no virological failure or transient episodes of low-level viremia were observed. At month 12, no significant changes were observed in total lymphocyte CD4 + count (855 c/µL vs 820 c/µL), CD4 + /CD8 + ratio (1.05 vs 1.07), IL-6 (2.24 pg/mL vs 2.24 pg/mL) and IP-10 (188.2 pg/mL vs 245.8 pg/mL). On the contrary, increased plasma concentrations of MIG (2785 pg/mL vs 2966 pg/mL, p = 0.017) and IL-18 (63.33 pg/mL vs 75.10 pg/mL, p = 0.009) were observed. In this respect, the variations in IL-18 concentrations were not correlated with significant changes concerning IL-18BP (59.26 pg/mL vs 43.34 pg/mL). Conclusions At 12 months after switching to a 2DR, plasma IL-18 and MIG concentrations increased, whereas IL-6 and IP-10 remained stable. The rise in IL-18 occurred independently of IL-18BP changes, indicating that reduced IL-18 neutralization is unlikely to explain this finding and supporting the involvement of alternative regulatory pathways.