Multiparametric Immune Profiles and Their Potential Role in HIV-1 Disease Progression and Treatment

<b>Backgrounds:</b> The rapid initiation of highly active anti-retroviral therapy (HAART) can control HIV-1 viremia and stabilize the long-term health of people living with HIV-1 (PLWH). Despite this, individuals who are diagnosed late and exhibit poor therapeutic efficacy still pose a great challenge to global HIV management. To address this, we conducted comprehensive multiparametric immune profiling and analyzed its association with disease progression and therapeutic efficacy. <b>Methods:</b> Multicolor flow cytometry was used to characterize the circulating immune cell composition and cellular phenotypes in 40 treatment-naive individuals (16 chronic, 24 newly diagnosed), 26 HAART-treated individuals, and 18 healthy controls. Comparative analyses of T cell subsets, immune activation markers, and viral load signatures were performed, followed by network construction. We carried out principal component analysis and displayed the data by dimensionality reduction. <b>Results:</b> Persistent immune activation, dysregulated regulatory immunity, and aberrant memory differentiation markers were identified in T cells of HIV-1-infected individuals and were associated with disease progression. Additionally, HAART-treated patients which did not fully restore CD4 T cells exhibited higher levels of activated markers, suggesting possible biomarkers of therapeutic efficacy. <b>Conclusions:</b> This study describes changes in immune cell profiles throughout HIV-1 disease progression and explores suitable laboratory predictors for future clinical and therapeutic settings by monitoring pathological immune cell events.