title: Human immunodeficiency virus type 1 fitness is a determining factor in viral rebound and set point in chronic infection.
abstract: Human immunodeficiency virus type 1 (HIV-1) isolates from 20 chronically infected patients who participated in a structured treatment interruption (STI) trial were studied to determine whether viral fitness influences reestablishment of viremia. Viruses derived from individuals who spontaneously controlled viremia had significantly lower in vitro replication capacities than viruses derived from individuals that did not control viremia after interruption of antiretroviral therapy (ART), and replication capacities correlated with pre-ART and post-STI viral set points. Of note, no clinically relevant improvement of viral loads upon STI occurred. Virus isolates from controlling and noncontrolling patients were indistinguishable in terms of coreceptor usage, genetic subtype, and sensitivity to neutralizing antibodies. In contrast, viruses from controlling patients exhibited increased sensitivity to inhibition by chemokines. Sensitivity to inhibition by RANTES correlated strongly with slower replication kinetics of the virus isolates, suggesting a marked dependency of these virus isolates on high coreceptor densities on the target cells. In summary, our data indicate that viral fitness is a driving factor in determining the magnitude of viral rebound and viral set point in chronic HIV-1 infection, and thus fitness should be considered as a parameter influencing the outcome of therapeutic intervention in chronic infection.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 8091 Zurich, Switzerland. alexandra.trkola@usz.ch
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trkola
authors.forename: Herbert
authors.initials: H
authors.lastname: Kuster
authors.forename: Christine
authors.initials: C
authors.lastname: Leemann
authors.forename: Claudia
authors.initials: C
authors.lastname: Ruprecht
authors.forename: Beda
authors.initials: B
authors.lastname: Joos
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bonhoeffer
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002908:Chronic Disease; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors