title: Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration.
abstract: BACKGROUND
  Antiretroviral therapy (ART)-mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication.
  
  
  METHODS
  A total of 23 HIV type 1 (HIV-1)-infected, virologically suppressed subjects receiving ART (CD4(+) T-cell count, >450 cells/μL) were randomly assigned to have 180 μg/week (for arm A) or 90 μg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg-interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥ 400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed.
  
  
  RESULTS
  At week 12 of Peg-interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P < .0001). Over 24 weeks, both arms had lower proportions of subjects who had viral load, compared with the proportion of subjects in a historical control group (arm A, P = .0046; arm B, P = .0011). Subjects who had a sustained viral load of <400 copies/mL had decreased levels of integrated HIV DNA (P = .0313) but increased residual viral loads (P = .0078), compared with subjects who experienced end-point failure.
  
  
  CONCLUSIONS
  Peg-interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication.
  
  
  BACKGROUND
  NCT00594880.
authors.affiliation: 1HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Foulkes
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Papasavvas
authors.forename: Angela M
authors.initials: AM
authors.lastname: Mexas
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Lynn
authors.forename: Karam
authors.initials: K
authors.lastname: Mounzer
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Una
authors.initials: U
authors.lastname: O'Doherty
authors.forename: Jay
authors.initials: J
authors.lastname: Kostman
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D016662:Virus Integration / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a