title: Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV-1-Infected Patients Starting Efavirenz, Lopinavir-Ritonavir, or Atazanavir-Ritonavir Plus Tenofovir/Emtricitabine: Final 48-Week Results (The Advanz-3 Trial).
abstract: BACKGROUND
  Few randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens.
  
  
  METHODS
  Randomized, controlled, open-label, multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naive patients with <100 CD4 cells per cubic millimeter were randomly assigned in a 1:1:1 ratio to efavirenz (n = 29), atazanavir/ritonavir (n = 30), or lopinavir/ritonavir (n = 30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary end points were the proportion of patients with HIV-1 RNA <50 copies per milliliter, adverse events, disease progression, and death.
  
  
  RESULTS
  In the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was +193 (129-349) cells per microliter in the efavirenz arm, +197 (146-238) cells per microliter in the ritonavir-boosted atazanavir arm, and +205 (178-327) cells per microliter in the ritonavir-boosted lopinavir arm (P = 0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks {efavirenz, 85.71% [95% confidence interval (CI): 68.5 to 94.3]; atazanavir, 80% [95% CI: 62.7 to 90.5]; and lopinavir, 82.8% [95% CI: 65.5 to 92.4]; P = 0.88}. Bacterial translocation, inflammation, immune activation, and apoptotic markers, but not D-dimer, declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died.
  
  
  CONCLUSIONS
  The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).
authors.affiliation: *Group of Immune receptors of the Innate and Adaptive System, IDIBAPS, Barcelona, Spain; †Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; ‡Immunology Department, Hospital Clínic de Barcelona, Barcelona Spain, University of Barcelona, Barcelona, Spain; §Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; ‖Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; and ¶Hospital Germans Trias i Pujols, Irsicaixa, Universitat Autònoma de Barcelona, UVic, Badalona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.forename: Christian
authors.initials: C
authors.lastname: Manzardo
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.forename: Montserrat
authors.initials: M
authors.lastname: Loncà
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Adrian
authors.initials: A
authors.lastname: Curran
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Anna
authors.initials: A
authors.lastname: Cruceta
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
authors.forename: Iñaki
authors.initials: I
authors.lastname: Pérez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; C098320:efavirenz; D019438:Ritonavir