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

Andrea Cossarizza; Alessandro Cozzi-Lepri; Marco Mattioli; Annamaria Paolini; Anita Neroni; Sara De Biasi; Domenico Lo Tartaro; Rebecca Borella; Lucia Fidanza; Lara Gibellini; Barbara Beghetto; Enrica Roncaglia; Giulia Nardini; Jovana Milic; Marianna Menozzi; Gianluca Cuomo; Margherita Digaetano; Gabriella Orlando; Vanni Borghi; Giovanni Guaraldi; Cristina Mussini

doi:10.3389/fimmu.2023.1279390

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

Front Immunol. 2023 Oct 16:14:1279390. doi: 10.3389/fimmu.2023.1279390. eCollection 2023.

Authors

Andrea Cossarizza¹, Alessandro Cozzi-Lepri², Marco Mattioli¹, Annamaria Paolini¹, Anita Neroni¹, Sara De Biasi¹, Domenico Lo Tartaro¹, Rebecca Borella¹, Lucia Fidanza¹, Lara Gibellini¹, Barbara Beghetto³, Enrica Roncaglia³, Giulia Nardini³, Jovana Milic³, Marianna Menozzi⁴, Gianluca Cuomo⁴, Margherita Digaetano⁴, Gabriella Orlando⁴, Vanni Borghi⁴, Giovanni Guaraldi^{3

4}, Cristina Mussini^{3

4}

Affiliations

¹ Chair of Pathology and Immunology, University of Modena and Reggio Emilia School of Medicine, Modena, Italy.
² Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London (UCL), London, United Kingdom.
³ Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Clinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy.

Abstract

Background: The 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).

Methods: An 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.

Results: Between 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.

Conclusion: No 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 registration: https://clinicaltrials.gov, identifier NCT04054089.

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

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.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

CD4-CD8 Ratio
HIV Infections*
Humans
Interleukin-6
Lamivudine / therapeutic use
Tenofovir / therapeutic use

Substances

Interleukin-6
Tenofovir
Lamivudine

Associated data

ClinicalTrials.gov/NCT04054089

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by an unrestricted grant by Gilead Sciences.