Background
Persistent immune activation underlies the increased risk of comorbidities during HIV treatment. Limited evidence exists on whether initiating treatment with two drugs differs from three-drug regimens in this regard. Here, we investigated the effects of DTG/3TC vs. BIC/F/TAF on inflammatory signatures in a large prospective cohort of ART-naive people living with HIV (PWH).
Methods
We included PWH who initiated DTG/3TC or BIC/F/TAF within the Spanish CoRIS cohort and had available plasma samples at month 0 (before ART initiation) and month 24 (±6). We matched participants starting each regimen 1:1 by propensity score (PS). The covariates included age, sex, and baseline CD4/CD8 ratio and HIV-1 RNA. Proteomic profiling was performed by Proximity Extension Assay using an inflammation-specific panel (Olink Target 96 Inflammation). Differences between treatment groups and timepoints were analyzed by Welch two sample t-test and paired t-test, respectively. Gene Set Enrichment Analysis (GSEA) was performed to investigate differential pathways between groups. P-values were adjusted by false discovery rate (Benjamini & Hochberg).
Results
We analyzed 148 PS-matched participants and 78 proteins. The median age was 37 years, 92% male, 74% MSM, with a median baseline CD4 of 380 cells/μL and CD4/CD8 of 0.5. Differential expression analysis showed overexpression of 11 proteins in the BIC/F/TAF group at baseline. Notably, after two years of ART, these signals were no longer detectable. When compared separately, the expression of different sets of inflammatory proteins strongly decreased in both groups. Proteins such as CXCL9, CXCL11, and CD6 —associated with pathogen response— were underexpressed in both groups after two years of ART. Functional evaluation of differentially expressed proteins supported the relevance of biological processes such as cell adhesion, activation of T cells, and general activation of immune response.
Conclusions
After two years, the expression of different sets of inflammatory proteins significantly decreased in both ART groups. These molecules are involved in relevant functions related to inflammation. The higher baseline inflammation in the BIC/F/TAF group, which resolved after two years, suggests that factors associated with greater inflammation may influence regimen selection and that this therapy effectively neutralized the initial disparity.