Markers of inflammation and immune dysfunction and non-AIDS cancer risk in adults with HIV.

Introduction: We evaluated the association between pre-ART immune dysfunction and inflammation markers and the risk of non-AIDS cancer (NAC) in people with HIV (PWH) after starting ART.

Methods: In a case-cohort study nested within CoRIS, a cohort of ART-naïve PWH, who started ART during 2004-2020, we included 113 NAC cases and a random subcohort of 512 individuals without prior cancers and with at least one pre-ART blood sample. We assessed immune dysfunction (CD4+ and CD8+ cell count, CD4/CD8 ratio) and inflammation markers (interleukin-6 [IL-6], high-sensitivity C-reactive protein, D-Dimer, and soluble CD14). We estimated hazard ratios (HRs) for the association between markers quartiles and NAC risk using Prentice-weighted Cox models separately for each marker and including all markers simultaneously.

Results: Among 614 participants (87.1% men; median age 37.3 years; 23.8% with CD4+ ≥ 500 cells/µL), we observed that NAC risk was not associated with immune dysfunction markers, and it was positively associated with IL-6 and D-dimer. Adjusted HRs for IL-6 ranged from 1.77 (95%CI 0.75, 4.16) to 2.73 (1.09, 6.86), while HRs for D-dimer were 3.93 (1.75, 8.84) for the third and 2.94 (1.26, 6.86) for the fourth compared to the first quartile. When all markers were included, only D-dimer confirmed its association with NAC.

Conclusions: Pre-ART inflammation and altered coagulation, but not immune dysfunction markers, were associated with risk of NAC. Limitations include the low number of cancer cases, precluding cancer-specific analyses, and lack of information on relevant confounders, like oncogenic coinfections. Further research is needed to validate these findings.