Factors associated with oxidative stress in virologically suppressed people living with HIV on long-term antiretroviral therapy

Background: Oxidative stress (OS) is the imbalance between oxidant and antioxidant molecules, in favour of oxidants, that has been associated with an increased risk of morbidity and mortality in ART-treated people living with HIV (PLWH). We aimed to assess factors associated with OS in virologically suppressed PLWH on long-term modern ART.

Method: In this cross-sectional study we evaluated OS by measuring both the levels of derivatives-reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP). We also calculated the BAP/d-ROMs ratio, (OS index, OSi); a cut-off value < 7.3 indicated OS. Factors associated with OS markers were explored by linear regression model.

Results: We enrolled 299 experienced PLWH with virological suppression (HIV-RNA < 50cps/mL). The mean of the d-ROMs levels was 409 UCARR (95%CI 394-422), whereas the mean of the BAP levels was 1.809 µmol/L (95%CI 1706-1851). The OSi mean value was 4.84, and 91.6% of the participants were below the cut-off value. By regression analysis, higher production of oxidants was associated with female sex (p < 0.001), current exposition to PIs (p = 0.030) and HCV co-infection (p = 0.006). Higher antioxidant capacity was correlated with higher HDL levels (p = 0.001). A lower OSi was associated with female sex (p = 0.003) and the current use of triple vs. dual regimen (p = 0.036). The OSi correlated negatively with cholesterol levels (p = 0.002) and positively with HDL (p < 0.001).

Conclusions: Virologically suppressed PLWH on long-term ART showed a marked OS. Female sex, the exposure to PIs, and HCV co-infection were associated with higher oxidants, while higher HDL levels were linked to better antioxidant capacity. Interestingly, dual therapy, especially INSTI-based regimens, was associated with lower oxidative stress compared to triple therapy.