TY - JOUR
T1 - Safely, tolerability, and mechanisms of antiretroviral activity of pegylated interferon alfa-2a in HIV-1monoinfected participants
T2 - A phase II clinical trial
AU - Asmuth, David M.
AU - Murphy, Robert L.
AU - Rosenkranz, Susan L.
AU - Lertora, Juan J.L.
AU - Kottilil, Shyam
AU - Cramer, Yoninah
AU - Chan, Ellen S.
AU - Schooley, Robert T.
AU - Rinaldo, Charles R.
AU - Thielman, Nathan
AU - Li, Xiao Dong
AU - Wahl, Sharon M.
AU - Shore, Jessica
AU - Janik, Jennifer
AU - Lempicki, Richard A.
AU - Simpson, Yaa
AU - Pollard, Richard B.
N1 - Funding Information:
Financial support: Roche Pharmaceutical (supplied pegylated interferon alfa-2a [Pegasys]); Amgen (provided filgrastim); National Institutes of Health (NIH; grant 1U01-AI068636 to the AIDS Clinical Trials Group [ACTG], grant 1U01-AI068634 to the ACTG Statistical and Data Analysis Center, grant 1U01-AI069471 to Northwestern University, grant 1U01-AI069432 to University of California, San Diego, grant 1U01-AI069484 to Duke University, Immunology Support Laboratory grant 201IC001 to University of California, Davis, and Immunology Support Laboratory grant 204IC006 to University of Pittsburgh); Intramural Research Program of the NIH; National Institute of Dental and Craniofacial Research.
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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 μg 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 interferoninducible 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 log10 copies/mL (90% confidence interval [CI], 0.20-1.18 log10 copies/ mL) and -44 cells/μL (90% CI, -95 to 85 cells/μL), 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 log10 copies/ mL [90% CI, 0.06-0.91 log10 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 log10 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. Trial registration. ClinicalTrials.gov identifier: NCT00078442.
AB - 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 μg 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 interferoninducible 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 log10 copies/mL (90% confidence interval [CI], 0.20-1.18 log10 copies/ mL) and -44 cells/μL (90% CI, -95 to 85 cells/μL), 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 log10 copies/ mL [90% CI, 0.06-0.91 log10 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 log10 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. Trial registration. ClinicalTrials.gov identifier: NCT00078442.
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U2 - 10.1086/652420
DO - 10.1086/652420
M3 - Article
C2 - 20420510
AN - SCOPUS:77951889263
SN - 0022-1899
VL - 201
SP - 1686
EP - 1696
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -
