title: Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.
abstract: BACKGROUND
  To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection.
  
  
  METHODS
  Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed.
  
  
  RESULTS
  Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]).
  
  
  CONCLUSIONS
  Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.
authors.affiliation: Division of Infectious Diseases, University of California-Davis Medical School, 4150 V Street, Sacramento, CA 95817-1460, USA. david.asmuth@ucdmc.ucdavis.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenkranz
authors.forename: Juan J L
authors.initials: JJ
authors.lastname: Lertora
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Yoninah
authors.initials: Y
authors.lastname: Cramer
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Nathan
authors.initials: N
authors.lastname: Thielman
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Wahl
authors.forename: Jessica
authors.initials: J
authors.lastname: Shore
authors.forename: Jennifer
authors.initials: J
authors.lastname: Janik
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Yaa
authors.initials: Y
authors.lastname: Simpson
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D015088:2',5'-Oligoadenylate Synthetase; C100416:peginterferon alfa-2a