title: Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control.
abstract: Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintained CD4+ cell levels >200/mm(3) with stable or increasing trend, despite sustained VLs of 500-5000 copies/mL, for >2 years. Treatment-success patients had CD4+ cell counts >200/mm(3) with stable or increasing trend and VLs <50 copies/mL, for >2 years. Treatment-failure patients initially responded to HAART, followed by decreasing CD4+ cell counts and increasing VLs. Interferon-gamma production to gag and noncytolytic CD8+ cell suppressive activity were greater in discordant responders. Cellular activation was greatest in patients with treatment failure. All discordant responders had non-syncytium-inducing (CCR5-tropic) viruses. Viruses from discordant responders and from patients with treatment failure had extensive resistance mutations; discordant responders had significantly lower viral replication capacities. These findings suggest that discordant responses may be related to enhanced HIV-directed immune responses, diminished cellular activation, decreased viral replication capacity, and preservation of non-syncytium-inducing virus strains.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Sufka
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Gryszowka
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Dhavalkumar D
authors.initials: DD
authors.lastname: Patel
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hellmann
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hicks
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D017320:HIV Protease Inhibitors