Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.

TitleSafety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.
Publication TypeJournal Article
Year of Publication2010
AuthorsAsmuth DM, Murphy RL, Rosenkranz SL, Lertora JJL, Kottilil S, Cramer Y, Chan ES, Schooley RT, Rinaldo CR, Thielman N, Li X-D, Wahl SM, Shore J, Janik J, Lempicki RA, Simpson Y, Pollard RB
Corporate AuthorsAIDS Clinical Trials Group A5192 Team
JournalJ Infect Dis
Volume201
Issue11
Pagination1686-96
Date Published2010 Jun 1
ISSN1537-6613
Keywords2',5'-Oligoadenylate Synthetase, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Gene Expression Profiling, HIV Infections, HIV-1, Humans, Interferon-alpha, Male, Middle Aged, Polyethylene Glycols, Recombinant Proteins, RNA, Viral, Treatment Outcome, Viral Load
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]).

CONCLUSION: 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.

DOI10.1086/652420
Alternate JournalJ. Infect. Dis.
PubMed ID20420510
PubMed Central IDPMC2946345
Grant List1U01-AI068634 / AI / NIAID NIH HHS / United States
1U01-AI068636 / AI / NIAID NIH HHS / United States
1U01-AI069432 / AI / NIAID NIH HHS / United States
1U01-AI069471 / AI / NIAID NIH HHS / United States
1U01-AI069484 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States