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Clinical Trial
. 2025 Feb 4;231(1):e91-e100.
doi: 10.1093/infdis/jiae405.

In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA)

Marie-Angélique De Scheerder  1 , Sophie Degroote  1 , Mareva Delporte  2 , Maja Kiselinova  1 , Wim Trypsteen  2   3 , Lara Vincke  1 , Evelien De Smet  2 , Bram Van Den Eeckhout  2   4 , Loïc Schrooyen  2 , Maxime Verschoore  2 , Camilla Muccini  5 , Sophie Vanherrewege  1 , Els Caluwe  1 , Stefanie De Buyser  6 , Sarah Gerlo  2   4 , Evy Blomme  2 , Linos Vandekerckhove  1   2
Affiliations
Clinical Trial

In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA)

Marie-Angélique De Scheerder et al. J Infect Dis. .

Abstract

Background: Reducing the number of active compounds for lifelong human immunodeficiency virus (HIV) treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control support the robustness and safety of 2DR (2-drug regimen) antiretroviral therapy compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts, and sustained immunological control.

Methods: The RUMBA study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable second-generation integrase strand transfer inhibitor-based 3DR regimen with HIV-1 RNA < 50 copies/mL plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, n = 89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n = 45). After 48 weeks, virological, immunological, and metabolic parameters were evaluated.

Results: We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in proinflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens.

Conclusions: This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription, and inflammatory markers.

Clinical trials registration: NCT04553081.

Keywords: HIV-1 reservoir; dual ART; inflammation; metabolic health; switch randomized controlled trial.

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Conflict of interest statement

Potential conflicts of interest. M. D. S. has been granted speakers fees from Gilead Sciences, ViiV Healthcare, and MSD; and has received grants from MSD, ViiV Healthcare, and Gilead Sciences to conduct independent investigator-initiated research in the HIV field. L. V. has been granted speaker fees and support for research projects by ViiV Healthcare, Gilead Sciences, and Johnson and Johnson over the past 5 years. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/in-depth-analysis-of-the-hiv-reservoir-confirms-effectiveness-and-safety-of-dtg-3tc-in-a-phase-4-randomized-controlled-switch-trial-rumba
Figure 1.
Figure 1.
Intact HIV-1 DNA. A, The absolute change in the number of intact HIV-1 DNA copies between week 48 and baseline, after correction for DNA shearing (median and IQR are reported; whiskers represent 1.5 IQR). Graph based on complete cases B/F/TAF = 33, DTG/3TC = 72, with outliers >1.5 IQR excluded (B/F/TAF = 5, DTG/3TC = 6). B, The relative change of intact HIV-1 DNA copies per million CD4 T cells from baseline, after correction for DNA shearing. Estimated mean values are reported with upper and lower confidence interval limit estimates, calculated using an ordinary linear regression model applied to change from baseline in natural log-transformed imputed data. Multiple imputations analysis in the intention-to-treat exposed set (n = 130) adjusted for baseline response value, CD4 nadir, and time on antiretroviral therapy. The triangle symbol represents the observed median change. Closed dots contain measurements above the LOD; open dots contain measurements below the LOD, replaced by the LOD/2, adjusted for cell input and DNA shearing index. C, Dynamics of intact HIV-1 DNA in the 2 treatment arms expressed as log10 copies/million CD4+ T cells at baseline (day 0) and after 48 weeks. Abbreviations: 3TC, lamivudine; B, bictegravir; DTG, dolutegravir; F, emtricitabine; HIV-1, human immunodeficiency virus-1; IQR, interquartile range; LOD, limit of detection; TAF, tenofovir alafenamide.
Figure 2.
Figure 2.
Differences in body composition. The relative change of trunk lean mass (A) and fat percentage (B) from baseline. C, The relative change of fat percentage in the subgroup of participants with no previous TAF exposure. Multiple imputations analysis in the intention-to-treat exposed set (n = 130) adjusted for baseline response value, baseline regimen, and baseline BMI (A and B) and for baseline response value and baseline BMI (C). Abbreviations: BMI, body mass index; CI, confidence interval; TAF, tenofovir alafenamide.
See this image and copyright information in PMC

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