Pre-ART platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio and the risk of non-AIDS-events, AIDS-events and mortality in people with HIV

Background: – Among people-with-HIV (PWH) on antiretroviral therapy (ART), serious-non-AIDS-events (SNAEs) are linked to inflammation. Neutrophil-to-lymphocyte-ratio (NLR), platelet-to-lymphocyte-ratio (PLR) and lymphocyte-to-monocyte-ratio (LMR) are inflammatory biomarkers. We investigated their performance in PWH.Material and methods: – PWH enrolled in the national cohort ICONA who started ART over 1997-2021 with measures of NLR, PLR and/or LMR within six months pre-ART (“baseline”) were included. Biomarkers were grouped using tertiles of their distribution (Q1, Q2, Q3). Association between baseline biomarkers values and risk of SNAEs, AIDS and all-cause mortality were tested using Kaplan-Meier and Cox proportional hazard models adjusting for baseline age, CD4+ count, HIV-RNA, HCV-status, and year of starting ART.Results: – We included 9, 248, 8, 727 and 1, 090 individuals in the PLR, NLR and LMR analyses, respectively: 77% male, median age 38. Baseline PLR, NLR and LMR mean values were 248.9, 2.7, and 8.2, respectively. After adjusting for confounders, the risk of SNAEs was higher for Q1-PLR vs Q2 and Q3 (adjusted-HR 0.76 [95%CI 0.64-0.90] and 0.78 [95%CI 0.66-0.94], respectively), as well as mortality (adjusted-HR 0.54 [95%CI 0.41-0.70], and 0.68 [95%CI 0.53-0.87], respectively), and the risk of AIDS was lower for Q2-PLR (adjusted-HR=0.74, 95%CI 0.60-0.90). Mortality was higher for Q3-NLR (adjusted-HR 1.32 [95%CI 1.01-1.72]). Q1-LMR showed higher risks of SNAEs, AIDS, and mortality, but this weakened after adjusting for confounders.Conclusions: – A baseline PLR below 93.2 was associated with SNAEs, AIDS and mortality and NLR above 2.04 was associated with mortality. Derived from routinely collected blood parameters, PLR and NLR may help clinicians identifying PWH at risk of poor outcomes, although these findings require external validation.