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Randomized Controlled Trial
. 2023 Oct 16:14:1279390.
doi: 10.3389/fimmu.2023.1279390. eCollection 2023.

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  1 , Alessandro Cozzi-Lepri  2 , Marco Mattioli  1 , Annamaria Paolini  1 , Anita Neroni  1 , Sara De Biasi  1 , Domenico Lo Tartaro  1 , Rebecca Borella  1 , Lucia Fidanza  1 , Lara Gibellini  1 , Barbara Beghetto  3 , Enrica Roncaglia  3 , Giulia Nardini  3 , Jovana Milic  3 , Marianna Menozzi  4 , Gianluca Cuomo  4 , Margherita Digaetano  4 , Gabriella Orlando  4 , Vanni Borghi  4 , Giovanni Guaraldi  3   4 , Cristina Mussini  3   4
Affiliations
Randomized Controlled Trial

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 et al. Front Immunol. .

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.

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Conflict of interest statement

GG and CM received a research grant and a speaker honorarium from Gilead, ViiV, MERCK, and Jansen. GG and CM are on the advisory boards of Gilead, ViiV, and MERCK. JM received a speaker honorarium from Gilead and ViiV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Box plots of CD4 and CD8 count subsets and adjusted prediction with 95% CI from fitting the mixed-linear model.
See this image and copyright information in PMC

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