Virologic and immunologic activity of PegIntron in HIV disease.
OBJECTIVE
The primary objectives of this study were to evaluate the safety, tolerability, and antiviral activity of pegylated interferon-alpha (PegIntron) in HIV-1 treatment-experienced patients failing their current antiretroviral regimen.


METHODS
This was a phase II, multicenter, randomized, double-blind, placebo-controlled study.


METHODS
Patients were randomized to receive either weekly subcutaneous PegIntron 0.5, 1.0, 1.5, or 3 microg/kg or placebo added to their failing antiretroviral regimen for the first 4 weeks of study. Individuals who achieved more than 0.5 log10 reduction in HIV RNA at week 4 were allowed to continue study medication with optimization of their antiretroviral therapy for an additional 24 weeks.


RESULTS
In the 259 patients included in the intent-to-treat analysis, changes in plasma HIV RNA from baseline to week 4 were -0.25 (P > 0.5), -0.46 (P = 0.024), -0.39 (P = 0.008), -0.53 (P < 0.001), and -0.17 (P > 0.5) log10 copies/ml in the 0.5, 1.0, 1.5, and 3.0 microg/kg and placebo arms, respectively. No significant changes were seen in CD4 T-cell parameters in any of the treatment or control arms. Adverse events (most commonly fever, flu-like symptoms, other constitutional symptoms, and psychiatric symptoms) resulted in discontinuation of study medication in 13, 17, 16, 28, and 2% of patients in the 0.5, 1.0, 1.5, 3.0 microg/kg, and placebo group, respectively.


CONCLUSIONS
The demonstration of significant antiviral activity in a heavily pretreated patient population with acceptable toxicity and only weekly dosing makes PegIntron a potentially valuable therapy for patients with HIV infection that warrants further investigation in a broader population of patients.
Angel
Jonathan B
JB
Ottawa Health Research Institute and the Department of Medicine, University of Ottawa, Ottawa, Canada. jangel@ohri.ca
Greaves
Wayne
W
Long
Jianmin
J
Ward
Douglas
D
Rodriguez
Allan E
AE
Scevola
Daniele
D
DeJesus
Edwin
E
D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D014481:United States
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b