Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial

Frontiers in Immunology

Immunology

Alessandro Cozzi-Lepri¹  Anita Neroni²  Marco Mattioli²  Andrea Cossarizza²  Lucia Fidanza²  Annamaria Paolini²  Lara Gibellini²  Domenico Lo Tartaro²  Sara De Biasi²  Rebecca Borella²  Gabriella Orlando³  Gianluca Cuomo³  Margherita Digaetano³  Vanni Borghi³  Marianna Menozzi³  Jovana Milic⁴  Barbara Beghetto⁴  Enrica Roncaglia⁴  Giulia Nardini⁴  Giovanni Guaraldi⁵  Cristina Mussini⁵ 

[1] Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London (UCL), London, United Kingdom;Chair of Pathology and Immunology, University of Modena and Reggio Emilia School of Medicine, Modena, Italy;Clinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy;Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy;Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy;Clinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy;

关键词: HIV;    dual regimen;    three-drug regimen;    DTG/3TC;    B/F/TAF;    CD4/CD8 ratio;   

DOI  :  10.3389/fimmu.2023.1279390

 received in 2023-08-18, accepted in 2023-09-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).MethodsAn open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.ResultsBetween the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = −6.7 cells/mm3; 95% CI; −16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.ConclusionNo evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT04054089.

【 授权许可】

Unknown   
Copyright © 2023 Cossarizza, Cozzi-Lepri, Mattioli, Paolini, Neroni, De Biasi, Tartaro, Borella, Fidanza, Gibellini, Beghetto, Roncaglia, Nardini, Milic, Menozzi, Cuomo, Digaetano, Orlando, Borghi, Guaraldi and Mussini