title: Immune reconstitution in severely immunosuppressed antiretroviral-naive HIV type 1-infected patients using a nonnucleoside reverse transcriptase inhibitor-based or a boosted protease inhibitor-based antiretroviral regimen: three-year results (The Advanz Trial): a randomized, controlled trial.
abstract: Late diagnosis of HIV-1 infection is quite frequent in Western countries. Very few randomized clinical trials to determine the best antiretroviral treatment in patients with advanced HIV-1 infection have been performed. To compare immune reconstitution in two groups of very immunosuppressed (less than 100 CD4(+) cells/microl), antiretroviral-naive HIV-1-infected adults, 65 patients were randomly assigned in a 1:1 ratio to receive zidovudine + lamivudine + efavirenz (group A, 34 patients) or zidovudine + lamivudine + ritonavir-boosted indinavir (group B, 31 patients). The median (interquartile range) CD4(+) cell increase after 12 and 36 months was +199 (101, 258) and +299 (170, 464) cells/microl in the efavirenz arm and +136 (57, 235) and +228 (119, 465) cells/microl in the ritonavir-boosted indinavir arm (p > 0.05 for all time points). The proportion (95% confidence interval) of patients achieving HIV-1 RNA levels under 50 copies/ml was significantly greater in the efavirenz arm at 3 years by the intention-to-treat analysis [59% (41%, 75%) vs. 23% (10%, 41%)], whereas no differences were found in the on-treatment analysis. Immune activation (CD8(+)CD38(+) and CD8(+)CD38DR(+) T cells) was significantly lower for the efavirenz arm from month 6 to month 24. Adverse events were more frequent in the ritonavir-boosted indinavir arm. Almost all cases of disease progression and death were observed in the first year of treatment, with no significant differences between the two arms (p = 0.79 by the log-rank test). At 1 and 3 years, the immune reconstitution induced by an efavirenz-based regimen in very immunosuppressed patients was at least as potent as that induced by a ritonavir-boosted protease inhibitor-based antiretroviral regimen.
authors.affiliation: Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain. jmmiro@ub.edu
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Christian
authors.initials: C
authors.lastname: Manzardo
authors.forename: Judith
authors.initials: J
authors.lastname: Pich
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Esteban
authors.initials: E
authors.lastname: Ribera
authors.forename: Julio
authors.initials: J
authors.lastname: Arrizabalaga
authors.forename: Montserrat
authors.initials: M
authors.lastname: Loncá
authors.forename: Anna
authors.initials: A
authors.lastname: Cruceta
authors.forename: Elisa
authors.initials: E
authors.lastname: de Lazzari
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fuster
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors