Evaluation of HIV Antiretroviral Therapy, Residual Viremia, and Immune Replacement as Possible Factors that Can Affect Systemic Inflammation

Background: The increase of age-related comorbidities is worrisome in HIV-infected patients. Its explanation is unclear even if multiple factors may apply, including the residual immune dysregulation syndrome and antiretrovirals alone. Despite many researchers are focusing on this topic, predictive biomarkers to evaluate chronic inflammation and ageing in HIV-infected patients have not been fully explored. Materials/methods: We evaluated the level of chronic inflammation and immune activation in 54 HIV virologically suppressed patients in relation to: 1. third drug associated to backbone: NNRTI (Group 1), PI (Group 2) and INI (Group 3); 2. Level of virological suppression: HIV-RNAq not detectable (Group 4) and HIV-RNAq <20 cp/ml (Group 5); 3. CD4+/CD8+>1 (Group 6) and CD4+/CD8+<1 (Group 7). A panel comprising 27 cytokines, chemokines and growth factors was tested by luminex multipanel technology. The software GraphPad Prism (v. 6) was used for statistical data analysis. Comparisons between two groups were made using the Mann-Whitney test. The Kruskall-Wallis one-way analysis of variance was used to compare more than two groups. When a significant p-value was found (p<0.05), a multiple comparison test was used to determine which groups were different. Results: Levels of inflammatory cytokine (IL-1, IL-6, IL-12, TNF-α), monocyte-derived chemokines (IL-8, MIP-1, MCP-1) were less represented in patients treated with INIs rather than NNRTIs and PIs with a statistically significant difference (p<0.05). A similar behavior was found for VEGF, although no significance was achieved in this case. Any difference in serum values was found between groups 4 and 5 for none of the tested mediators. Finally, considering the CD4+/CD8+ ratio as the last stratification criterion, Group 7 showed higher levels of inflammatory mediators compared to Group 6 but without any statistical significance. Conclusions: The type of antiretroviral regimen and the level of immunosuppression, in terms of CD4+/CD8+ ratio, are both factors that may affect systemic inflammation in HIV positive subjects with suppressed viremia. Furthermore, since monocytes are key cells in the atherosclerotic process and many of the tested chemokines are monocyte-derived, such mediators could be promising as predictors of cardiovascular risk in HIV positive patients. More studies are needed to further investigate their role.