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, Alexis Inciarte, Cristina Rovira, Anna Cruceta, Carmen Hurtado, Núria Climent, Francisco Lozano, Montserrat Plana
{"title":"以多替格拉韦与达若那韦为基础的三联抗逆转录病毒疗法治疗的晚期HIV患者的免疫重建Advanz-4随机临床试验。","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, Alexis Inciarte, Cristina Rovira, Anna Cruceta, Carmen Hurtado, Núria Climent, Francisco Lozano, Montserrat Plana","doi":"10.1016/j.cmi.2025.09.026","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Phase IV, randomized (1:1 ratio), open-label trial, including adult (≥18 years) ART-naïve HIV-1+ patients with CD4<sup>+</sup> cell counts <100 cells/ L from nine hospitals in Spain. Participants were randomized to Lamivudine (3TC)/Abacavir (ABC)/DTG (DTG arm) and 3TC/ABC/DRV + Ritonavir (DRV/r arm).</p><p><strong>Primary endpoint: </strong>change in the absolute CD4<sup>+</sup>-cells number at 48 weeks. by modified intention-to-treat population.</p><p><strong>Trial registration: </strong>NCT02337322.</p><p><strong>Results: </strong>104 patients (86·5% male, median [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<sup>+</sup> cell counts were 41·0 (18·5, 67·5) and 30·0 (11·0, 57·5) cells/ L in the DTG and DRV/r arms. They significantly increased by median (IQR) 172·5 (118·0, 255·3) and 157·0 (66·0, 276·9) cells/ L, respectively (p=0·4299); 29 (55·8%) and 21 (42·9%) (p=0·2343), respectively, reached >200 cells/ L. 41 (78·8%) and 31 (63·3%) patients (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=0·0190). Inflammation (TNF-alpha) and bacterial translocation (sCD14) markers decreased more in the DTG arm, a 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).</p><p><strong>Conclusions: </strong>DTG/3TC/ABC is safe and efficacious in very advanced ART-naïve HIV+ patients, induced a faster virological response, and was superior to the DRV/r regimen in reducing inflammation and bacterial translocation markers at 48 weeks.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":8.5000,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immune reconstitution in very advanced HIV patients treated with Dolutegravir vs Darunavir-based triple antiretroviral therapy. The Advanz-4 randomized clinical trial.\",\"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, Alexis Inciarte, Cristina Rovira, Anna Cruceta, Carmen Hurtado, Núria Climent, Francisco Lozano, Montserrat Plana\",\"doi\":\"10.1016/j.cmi.2025.09.026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Phase IV, randomized (1:1 ratio), open-label trial, including adult (≥18 years) ART-naïve HIV-1+ patients with CD4<sup>+</sup> cell counts <100 cells/ L from nine hospitals in Spain. Participants were randomized to Lamivudine (3TC)/Abacavir (ABC)/DTG (DTG arm) and 3TC/ABC/DRV + Ritonavir (DRV/r arm).</p><p><strong>Primary endpoint: </strong>change in the absolute CD4<sup>+</sup>-cells number at 48 weeks. by modified intention-to-treat population.</p><p><strong>Trial registration: </strong>NCT02337322.</p><p><strong>Results: </strong>104 patients (86·5% male, median [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<sup>+</sup> cell counts were 41·0 (18·5, 67·5) and 30·0 (11·0, 57·5) cells/ L in the DTG and DRV/r arms. They significantly increased by median (IQR) 172·5 (118·0, 255·3) and 157·0 (66·0, 276·9) cells/ L, respectively (p=0·4299); 29 (55·8%) and 21 (42·9%) (p=0·2343), respectively, reached >200 cells/ L. 41 (78·8%) and 31 (63·3%) patients (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=0·0190). Inflammation (TNF-alpha) and bacterial translocation (sCD14) markers decreased more in the DTG arm, a 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).</p><p><strong>Conclusions: </strong>DTG/3TC/ABC is safe and efficacious in very advanced ART-naïve HIV+ patients, induced a faster virological response, and was superior to the DRV/r regimen in reducing inflammation and bacterial translocation markers at 48 weeks.</p>\",\"PeriodicalId\":10444,\"journal\":{\"name\":\"Clinical Microbiology and Infection\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2025-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Microbiology and Infection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmi.2025.09.026\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Microbiology and Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.cmi.2025.09.026","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Immune reconstitution in very advanced HIV patients treated with Dolutegravir vs Darunavir-based triple antiretroviral therapy. The Advanz-4 randomized clinical trial.
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/ L 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+-cells number at 48 weeks. by modified intention-to-treat population.
Trial registration: NCT02337322.
Results: 104 patients (86·5% male, median [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 41·0 (18·5, 67·5) and 30·0 (11·0, 57·5) cells/ L in the DTG and DRV/r arms. They significantly increased by median (IQR) 172·5 (118·0, 255·3) and 157·0 (66·0, 276·9) cells/ L, respectively (p=0·4299); 29 (55·8%) and 21 (42·9%) (p=0·2343), respectively, reached >200 cells/ L. 41 (78·8%) and 31 (63·3%) patients (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=0·0190). Inflammation (TNF-alpha) and bacterial translocation (sCD14) markers decreased more in the DTG arm, a 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 virological response, and was superior to the DRV/r regimen in reducing inflammation and bacterial translocation markers at 48 weeks.
期刊介绍：
Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
