title: Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease.
abstract: Highly active antiretroviral therapy (HAART) of HIV disease is associated with effective virologic control, immune reconstitution, and clinical improvements. This study addresses the potential for improvements in lymphocyte phenotype and virologic responses of HIV-infected persons with extensive experience with dual nucleoside reverse transcriptase (NRTI) treatment and advanced HIV disease after a change to a potent antiretroviral therapy (NRTI + protease inhibitor). The majority of participants achieved virologic success. There was a median rise in CD4+ lymphocytes of 99 cells/mm(3) by 48 weeks, because of an increase in memory CD4+ cells at 4 and 16 weeks, followed by a later increase in naive CD4+ cells between weeks 16 and 48. The proportion of activated, DR+ CD38+ CD8+ lymphocytes decreased during the 48 weeks of follow-up. The immunologic findings (increased memory and naive T cells and reduced activation levels) were significantly improved in participants with persistent suppression of viral replication over the 48 weeks of the study. Baseline HIV RNA copy number was lower (median, 14,784 copies/ml) in persons who responded virologically than in those not suppressing viral replication (median, 49,454 copies/ml). CD4+ cell counts above the median (125/mm(3)) at time 0 for the participants, was the only baseline immunologic marker significantly associated with viral suppression at week 48. Participants older than 40 years of age demonstrated less immunologic recovery. The results of the study show that patients with extensive experience with NRTIs respond both virologically and immunologically during the first 48 weeks of therapy with a potent antiretroviral regimen.
authors.affiliation: Department of Immunology/Microbiology, Rush Medical College, Chicago, Illinois 60612, USA. alanday@rush.edu
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Daniel
authors.initials: D
authors.lastname: Bettendorf
authors.forename: Ellen
authors.initials: E
authors.lastname: Chan
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: John L
authors.initials: JL
authors.lastname: Schmitz
authors.forename: R Pat
authors.initials: RP
authors.lastname: Bucy
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Gonzalez
authors.forename: Carol T
authors.initials: CT
authors.lastname: Schnizlein-Bick
authors.forename: Tom
authors.initials: T
authors.lastname: Evans
authors.forename: Kate E
authors.initials: KE
authors.lastname: Squires
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D003521:Cyclopropanes; D016049:Didanosine / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D015703:Antigens, CD; D048588:Benzoxazines; D015415:Biomarkers; D003521:Cyclopropanes; D016049:Didanosine; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019259:Lamivudine; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz