Finally, HIV-1 infection is characterized by persi

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Finally, HIV-1 infection is characterized by persistent elevation of type I and II interferons. It has been demonstrated that inadequate regulation of IFN responses drives chronic immune activation [29,30].

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Indeed, many studies report uncommon levels of many cytokines, such as pro-inflammatory IL-1β, IL-2, IL-6, IL-8, and TNF-α, but also anti-inflammatory cytokines, such as IL-4, IL-10, and IL-13. Moreover, increased levels of MIP-1α, ICAM, VCAM, MCP-1, and CXCL9 were found

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For example, levels of several pro-inflammatory molecules, such as CRP, IL-6, and D-dimer [75], as well as markers of T-cell activation [76,77], remain higher in PLWH than in uninfected controls despite suppressive cART, and this increase has been associated with higher mortality

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In cART-treated patients, levels of pro-inflammatory cytokines are also associated with increased risk of CVD, independently from other CVD risk factors [84,85], and with infection-related and unrelated cancers, even after adjusting for demographics and CD4+ T cell counts [86]. In addition, higher levels of TNF-α were also found to be significantly associated with the occurrence of serious non-AIDS events

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Due to the well-known anti-inflammatory properties of statins reducing the release of pro-inflammatory cytokines at the vessel level, these anti-cholesterol agents were also used in several trials in PLWH with cART, aimed at reducing inflammation and immune activation at different stages of viral infection. A reduction in circulating activated CD4+ and CD8+ T cell subsets (i.e., HLA-DR+ and CD38+ expressing cells) was observed, whereas no statistically significant changes were reported for levels of pro-inflammatory cytokines

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A variable proportion of individuals fails to achieve a CD4+ T cell number above 500/μL, despite chronic suppression of HIV-1 replication, and this suboptimal recovery increases the risk of many comorbidities (heart, renal, metabolic, bone diseases, and cancers) as well as all-cause mortality.

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