Journal Article

Long-term effects on immunological, inflammatory markers, and HIV-1 reservoir after switching to a two-drug versus maintaining a three-drug regimen based on integrase inhibitors

Sotomayor, Cesar, Herrero, Marta, Serna-Gallego, Ana, Lopez-Cortes, Luis F., Espinosa, Nuria, Muñoz-Muela, Esperanza, Gutierrez-Valencia, Alicia, Lozano, Carmen, Trujillo-Rodriguez, María, Álvarez-Ríos, Ana I., Saborido-Alconchel, Abraham, Llaves-Flores, Silvia, Roca-Oporto, Cristina

2024

Overview

To compare the long-term effects on immune parameters, inflammation, and HIV-1 reservoir after switching to a two-drug (2DR) versus maintaining an integrase inhibitor (InSTI)-based three-drug regimen (3DR). Cross-sectional study in which HIV-1 treatment-naïve people started and maintained an InSTI-based 3DR or, at different times, switched to 2DR (dolutegravir or darunavir/cobicistat + lamivudine). CD4 and CD8 T-cell activation and exhaustion, plasma concentrations of hs-CRP, D-dimer, P-selectin, IL-1β, IL-6, TNF-α, IFN-γ, IP-10, sTNFR-I/II, MIP-1α/β, I-FABP, LBP, sCD14, sCD163, MCP-1, and cellular-associated HIV-1-DNA and -RNA were quantified by flow cytometry, different immunoassays, and droplet digital PCR, respectively. The U de Mann-Whitney test evaluated differences between 3DR and 2DR. Immune recovery was evaluated using a general linear model for repeated measures adjusted for different co-variables. Fifty participants per group were included. The median time on 3DR was 82 months for the 3DR group and 30 months for the 2DR group, after which it switched to 2DR for a median of 57 months. We did not find differences between both groups in any of the parameters analyzed. Specifically, some values in 3DR and 2DR were hs-CRP, 0.92 mg/L (0.45-2.23) vs. 1.23 (0.61-2.38); D-dimer, 190.0 µg/L (150.0-370.0) vs. 190.0 (150.0-397.5); IL-6, 2.8 pg/mL (1.3-5.3) vs. 3.2 (2.1-4.7); sCD14, 4.5 ng/mL (3.3-6.2) vs. 5.0 (3.6-6.1), respectively, all p ≥ 0.399. In the long term, switching to 2DR does not negatively affect immunologic parameters, inflammatory markers, or HIV-1 reservoir. identifier NCT04076423.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adult / antiretroviral therapy / Biomarkers - blood / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Cell activation / Cross-Sectional Studies / dual therapy / Fatty acid-binding protein / Female / Flow cytometry / HIV / HIV Infections - blood / HIV Infections - drug therapy / HIV Infections - immunology / HIV Infections - virology / HIV Integrase Inhibitors - therapeutic use / HIV-1 - drug effects / HIV-1 - immunology / HIV-1 infection / HIV-1 treatment / Human immunodeficiency virus / Humans / Immunology / Inflammation / Inflammation - immunology / Integrase / Interleukin 6 / IP-10 protein / Lamivudine / long-term / Long-term effects / Lymphocytes T / Male / Middle Aged / Monocyte chemoattractant protein 1 / Oxazines - therapeutic use / P-selectin / Plasma / Proteins / Software / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Variables / Viral Load / γ-Interferon