Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2025
Immune reconstitution in very advanced HIV patients treated with dolutegravir vs. darunavir-based triple antiretroviral therapy: the Advanz-4 randomized clinical trial.
СтатьяРандомизированное исследованиеКлиническое исследование IV фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Miro Jose M, Torres Ferran, Manzardo Christian, Bonfill Eva, Curran Adrià, Domingo Pere, Podzamczer Daniel, Paredes Roger, Force Lluis, Falco Vicenç, Gutierrez Mar, Saumoy Maria, Castelli Anna, Inciarte Alexy, Rovira Cristina, Cruceta Anna, Hurtado Carmen, Climent Núria, Lozano Francisco, Plana Montserrat, Advanz-4 investigators
Аннотация
OBJECTIVES: The aim of this trial was to compare the immune reconstitution, virologic response, and safety of dolutegravir (DTG) vs. darunavir (DRV) boosted-based antiretroviral (ART) regimens in very advanced HIV patients.
METHODS: Phase IV, randomized (1:1 ratio), open-label trial, including adult (≥18 years) ART-naïve HIV-1+ patients with CD4+ cell counts <100 cells/μL from nine hospitals in Spain. Participants were randomized to lamivudine (3TC)/abacavir (ABC)/DTG (DTG arm) and 3TC/ABC/DRV + ritonavir (DRV/r arm).
PRIMARY ENDPOINT: change in the absolute CD4+ cell number at 48 weeks in the modified intention-to-treat population.
TRIAL REGISTRATION: NCT02337322.
RESULTS: In total, 104 patients (86.5% male, median (interquartile range [IQR]) age 41.0 (31.5, 47.0) years) were recruited and randomized to DTG (n = 52) and DRV/r arms (n = 52). Baseline median (IQR) CD4+ cell counts were 39.5 (16.0, 72.9) and 29.0 (8.0, 60.0) cells/μL in the DTG and DRV/r arms. They significantly increased by median (IQR) 206.5 (154.4, 310.5) and 180.0 (89.4, 314.0) cells/μL, respectively (p 0.2549); 29 (55.8%) and 21 (42.9%) (p 0.2343) patients, respectively, reached >200 cells/μL. Of the patients, 41 (78.8%) and 31 (63.3%) (p 0.1229) in the DTG and DRV/r arms, respectively, achieved undetectable viral loads at 48 weeks; differences were significant at weeks 4 (p < 0.0001) and 12 (p 0.0009). Inflammation and bacterial translocation markers decreased more in the DTG arm, median (IQR) -8 (-11, -4) vs. -5 (-9, -3) pg/mL (p 0.0357) and -972 (-1334, -508) vs. -544 (-1128, -292) μg/mL (p 0.0565), respectively, at 48 weeks. Discontinuation rates were higher in the DRV/r arm (3/52 (5.8%) vs. 9/51 (18.4%); p 0.0526).
CONCLUSIONS: DTG/3TC/ABC is safe and efficacious in very advanced ART-naïve HIV + patients, induced a faster virologic response, and was superior to the DRV/r regimen in reducing inflammation and bacterial translocation markers at 48 weeks.
METHODS: Phase IV, randomized (1:1 ratio), open-label trial, including adult (≥18 years) ART-naïve HIV-1+ patients with CD4+ cell counts <100 cells/μL from nine hospitals in Spain. Participants were randomized to lamivudine (3TC)/abacavir (ABC)/DTG (DTG arm) and 3TC/ABC/DRV + ritonavir (DRV/r arm).
PRIMARY ENDPOINT: change in the absolute CD4+ cell number at 48 weeks in the modified intention-to-treat population.
TRIAL REGISTRATION: NCT02337322.
RESULTS: In total, 104 patients (86.5% male, median (interquartile range [IQR]) age 41.0 (31.5, 47.0) years) were recruited and randomized to DTG (n = 52) and DRV/r arms (n = 52). Baseline median (IQR) CD4+ cell counts were 39.5 (16.0, 72.9) and 29.0 (8.0, 60.0) cells/μL in the DTG and DRV/r arms. They significantly increased by median (IQR) 206.5 (154.4, 310.5) and 180.0 (89.4, 314.0) cells/μL, respectively (p 0.2549); 29 (55.8%) and 21 (42.9%) (p 0.2343) patients, respectively, reached >200 cells/μL. Of the patients, 41 (78.8%) and 31 (63.3%) (p 0.1229) in the DTG and DRV/r arms, respectively, achieved undetectable viral loads at 48 weeks; differences were significant at weeks 4 (p < 0.0001) and 12 (p 0.0009). Inflammation and bacterial translocation markers decreased more in the DTG arm, median (IQR) -8 (-11, -4) vs. -5 (-9, -3) pg/mL (p 0.0357) and -972 (-1334, -508) vs. -544 (-1128, -292) μg/mL (p 0.0565), respectively, at 48 weeks. Discontinuation rates were higher in the DRV/r arm (3/52 (5.8%) vs. 9/51 (18.4%); p 0.0526).
CONCLUSIONS: DTG/3TC/ABC is safe and efficacious in very advanced ART-naïve HIV + patients, induced a faster virologic response, and was superior to the DRV/r regimen in reducing inflammation and bacterial translocation markers at 48 weeks.