# Different Trends of Immune Activation Markers When Switching to Either Oral or Injectable Dual Antiretroviral Therapy Based on Integrase Inhibitors in People Living with HIV

## TL;DR

This study compares immune activation in HIV patients switching to either oral or injectable dual therapy, finding different immune trends.

## Contribution

The study is the first to compare immune activation markers between oral and long-acting injectable dual ART simplification strategies in HIV patients.

## Key findings

- Switching to long-acting ART increased sCD14 levels, while oral ART decreased them.
- sCD163 levels increased in patients with low CD4 nadir or AIDS when switching to oral ART but not injectable ART.
- Changes in immune markers were not linked to microbial translocation or gut integrity markers.

## Abstract

Background: Despite improvements in life expectancy, people living with HIV (PWH) continue displaying immune activation and high rates of comorbid conditions. No comparative studies concerning activation markers exist between simplification strategies to either oral or long-acting (LA) dual ART. Methods: We prospectively collected plasma samples from PWH on successful ART, simplifying treatment from triple oral to either oral or LA dual ART based on integrase inhibitors. We measured changes in soluble CD14 (sCD14), soluble CD163 (sCD163), monocyte chemoattractant protein-1, and interleukin-6. Background measurements and markers of microbial translocation and gut integrity (I-FABP, LBP) were also collected. Results: From 2019 to 2023, 38 PWH were analyzed (mean age 52, 87% male, 21 years HIV diagnosis, CD4 730 cells/mm3, nadir CD4 317 cells/mm3, AIDS 13%). After 7.2 months, sCD14 trajectories differed according to regimen (+0.43 ng/mL, p = 0.033 for LA ART, −0.62 ng/mL, p < 0.001 for oral ART) but were not related to I-FABP or to LBP values. In case of CD4 nadir < 200 cc/mm3, AIDS, or very-low-level viremia, sCD163 values significantly increased when switching to oral but not to LA dual ART. Conclusion: We found different trends in immune activation markers and risk factors associated with PWH switching to either oral or LA ART, requiring larger studies.