Association of baseline plasma oxidative stress biomarkers with incident non-AIDS-defining cancer risk in people with HIV: a case-cohort study.

Abstract

People with HIV (PWH) receiving antiretroviral therapy (ART) exhibit an elevated risk of non-AIDS-defining cancers (NADCs). This case-cohort study evaluated the association of baseline plasma oxidative stress biomarkers with incident NADC risk in 332 PWH on ART from the Spanish HIV Research Network. Borgan II-weighted cause-specific Cox proportional hazards models assessed effect modification by sex and age. While no overall associations were observed between oxidative stress biomarkers and NADC risk, exploratory analyses revealed potential effect modification by sex and age. Increased 4-HNE levels were associated with higher NADC risk in females (aHR = 2.79 [95% CI, 1.14-6.80]) but not in males; however, this finding is exploratory given the small female sample (15.4%). Additionally, age modified the associations of 4-HNE and ox-LDL with NADC risk (interaction p < 0.050), although stratum-specific estimates in older adults (≥ 50 years) exhibited wide confidence intervals and did not achieve statistical significance. Integrating these biomarkers into a clinical model for older adults improved in-sample discrimination (C-index, 0.863 to 0.877; p = 0.003), with consistent incremental gains observed during internal fivefold cross-validation (out-of-fold C-index, 0.586 to 0.632). These exploratory findings suggest that lipid peroxidation biomarkers may be associated with NADC risk in selected subgroups, requiring validation in larger cohorts.