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Randomized Controlled Trial
. 2025 Mar 17;231(3):600-610.
doi: 10.1093/infdis/jiae530.

Impact of Dolutegravir Plus Lamivudine as First-line Antiretroviral Treatment on the Human Immunodeficiency Virus Type 1 Reservoir and Inflammatory Markers in Peripheral Blood

Lucía Bailón  1   2 , Maria C Puertas  3   4   5 , Maria C García-Guerrero  5 , Igor Moraes-Cardoso  3   5   6 , Ester Aparicio  5 , Yovaninna Alarcón-Soto  2 , Angel Rivero  1   2   7 , Elias P Rosen  8 , Jacob D Estes  9   10 , Julià Blanco  3   4   5   11 , Alex Olvera  4   5   11   12 , Beatriz Mothe  1   2   3   4   5   11 , Javier Martinez-Picado  4   5   11   13 , José Moltó  1   2   3   4 ; DUALITY Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Impact of Dolutegravir Plus Lamivudine as First-line Antiretroviral Treatment on the Human Immunodeficiency Virus Type 1 Reservoir and Inflammatory Markers in Peripheral Blood

Lucía Bailón et al. J Infect Dis. .

Abstract

Background: To compare the effects of first-line antiretroviral therapy (ART) with dolutegravir plus lamivudine (DTG + 3TC) versus dolutegravir plus emtricitabine/tenofovir alafenamide (DTG + FTC/TAF) on the human immunodeficiency virus type 1 (HIV-1) reservoir and immune activation biomarkers in people with HIV (PWH).

Methods: DUALITY was a 48-week, single-center, randomized, open-label clinical trial in ART-naive PWH, randomized (1:1) to receive ART with DTG + 3TC (2DR group) or DTG + FTC/TAF (3DR group). We measured total and intact proviral HIV-1 DNA, cell-associated RNA in CD4+ T cells, frequency of HIV-infected CD4+ T cells able to produce p24, plasma soluble inflammatory markers, and activation and exhaustion markers in CD4+ and CD8+ T cells.

Results: Forty-four participants (22 per study arm) were enrolled, with baseline mean (standard deviation) log10 plasma viral load (pVL) 4.4 (0.7) copies/mL and CD4+ T-cell counts of 493 (221) cells/μL. At week 48, all participants had pVL <50 copies/mL at week 48, except for 1 participant in the 2DR group who was resuppressed after treating syphilis. Changes from baseline in reservoir parameters and immune biomarkers were comparable between groups.

Conclusions: First-line ART with DTG + 3TC showed similar reductions of HIV-1 persistence parameters and immune markers as DTG + FTC/TAF, supporting DTG/3TC among preferred first-line ART options for PWH.

Keywords: HIV infection; HIV reservoir; dolutegravir/lamivudine; dual antiretroviral therapy; immune activation.

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Figures

Figure 1.
Figure 1.
Dynamics of plasma viral load during the study. A, Viral load measured using standard techniques: The percentage of participants reaching HIV-1 RNA <50 copies/mL at each time point is shown. B, Residual viremia: Individual determinations and medians for each study group are shown. Half of the lower limit of quantification (LLOQ) of this ultrasensitive quantification (0.33 copy/mL) was used to represent samples below LLOQ in the graph (open symbols). The gray dotted lines indicate the 50 copies/mL and the 0.33 copy/mL levels. Abbreviations: 2DR, 2-drug regimen (dolutegravir plus lamivudine); 3DR, 3-drug regimen (dolutegravir plus emtricitabine/tenofovir alafenamide); HIV-1, human immunodeficiency virus type 1; pVL, plasma viral load.
Figure 2.
Figure 2.
Evolution of viral reservoir parameters during the study. A, Total proviral HIV-1 DNA. B, Intact HIV-1 DNA copies. C, Cell-associated RNA. D, Viral protein spot (VIPSPOT) assay. Individual values are presented with their corresponding geometric mean and 95% confidence interval. Values below the lower limit of quantification (LLOQ) are represented as open circles. Abbreviations: 2DR, 2-drug regimen (dolutegravir plus lamivudine); 3DR, 3-drug regimen (dolutegravir plus emtricitabine/tenofovir alafenamide); HAP, human immunodeficiency virus antigen–producing; HIV-1, human immunodeficiency virus type 1; TBP, TATA-binding protein; VIP-SPOT, viral protein spot assay.
Figure 3.
Figure 3.
Changes from baseline in soluble inflammatory biomarkers during the study. Median and interquartile range are presented. Abbreviations: 2DR, 2-drug regimen (dolutegravir plus lamivudine); 3DR, 3-drug regimen (dolutegravir plus emtricitabine/tenofovir alafenamide); BL, baseline; CRP, C-reactive protein; DD, D-dimer; FABP2, fatty acid–binding protein 2; IL-6, interleukin 6; IP-10, interferon-γ–induced protein 10; sCD14, soluble CD14; TRAIL, tumor necrosis factor–related apoptosis-inducing ligand.
Figure 4.
Figure 4.
T-cell immune activation and exhaustion markers during the study. A and C, Activation and exhaustion markers in CD4+ T cells. B and D, Activation and exhaustion markers in CD8+ T cells. Individual values are presented with their corresponding median and interquartile range (IQR). E, Median and IQR changes from baseline. Abbreviations: 2DR, 2-drug regimen (dolutegravir plus lamivudine); 3DR, 3-drug regimen (dolutegravir plus emtricitabine/tenofovir alafenamide); BL, baseline.
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References

    1. Trickey A, Sabin CA, Burkholder G, et al. Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies. Lancet HIV 2023; 10:e295–307. - PMC - PubMed
    1. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet 2019; 393:2428–38. - PMC - PubMed
    1. Bailón L, Llano A, Cedeño S, et al. Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. Nat Med 2022; 28:2611–21. - PubMed
    1. Namazi G, Fajnzylber JM, Aga E, et al. The Control of HIV After Antiretroviral Medication Pause (CHAMP) study: posttreatment controllers identified from 14 clinical studies. J Infect Dis 2018; 218:1954–63. - PMC - PubMed
    1. Gálvez C, Grau-Expósito J, Urrea V, et al. Atlas of the HIV-1 reservoir in peripheral CD4 T cells of individuals on successful antiretroviral therapy. mBio 2021; 12:e0307821. - PMC - PubMed

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