Authors: Jose M. Miro, Ferran Torres, Christian Manzardo, Eva Bonfill, Adrià Curran, Pere Domingo, Daniel Podzamczer, Roger Paredes, Lluis Force, Vicenç Falco, Mar Gutierrez, Maria Saumoy, Anna Castelli, Alexy Inciarte, Cristina Rovira, Anna Cruceta, Carmen Hurtado, Núria Climent, Francisco Lozano, Montserrat Plana and the Advanz-4 investigators
Abstract: 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 HIV1+ 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, achieve 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
