Safely, tolerability, and mechanisms of antiretroviral activity of pegylated interferon alfa-2a in HIV-1monoinfected participants: A phase II clinical trial

David Asmuth, Robert L. Murphy, Susan L. Rosenkranz, Juan J L Lertora, Shyam Kottilil, Yoninah Cramer, Ellen S. Chan, Robert T. Schooley, Charles R. Rinaldo, Nathan Thielman, Xiao Dong Li, Sharon M. Wahl, Jessica Shore, Jennifer Janik, Richard A. Lempicki, Yaa Simpson, Richard B Pollard

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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 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.

Original languageEnglish (US)
Pages (from-to)1686-1696
Number of pages11
JournalJournal of Infectious Diseases
Volume201
Issue number11
DOIs
StatePublished - Jun 1 2010

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Phase II Clinical Trials
HIV-1
HIV
Viral Load
Confidence Intervals
Virus Diseases
Ligases
CD4 Lymphocyte Count
Hepacivirus
Interferons
Genes
T-Lymphocytes
Chronic Hepatitis C
peginterferon alfa-2a
Antiviral Agents
Volunteers
Pharmacokinetics
RNA
2',5'-oligoadenylate

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Medicine(all)

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Safely, tolerability, and mechanisms of antiretroviral activity of pegylated interferon alfa-2a in HIV-1monoinfected participants : A phase II clinical trial. / Asmuth, David; Murphy, Robert L.; Rosenkranz, Susan L.; Lertora, Juan J L; Kottilil, Shyam; Cramer, Yoninah; Chan, Ellen S.; Schooley, Robert T.; Rinaldo, Charles R.; Thielman, Nathan; Li, Xiao Dong; Wahl, Sharon M.; Shore, Jessica; Janik, Jennifer; Lempicki, Richard A.; Simpson, Yaa; Pollard, Richard B.

In: Journal of Infectious Diseases, Vol. 201, No. 11, 01.06.2010, p. 1686-1696.

Research output: Contribution to journalArticle

Asmuth, D, Murphy, RL, Rosenkranz, SL, Lertora, JJL, Kottilil, S, Cramer, Y, Chan, ES, Schooley, RT, Rinaldo, CR, Thielman, N, Li, XD, Wahl, SM, Shore, J, Janik, J, Lempicki, RA, Simpson, Y & Pollard, RB 2010, 'Safely, tolerability, and mechanisms of antiretroviral activity of pegylated interferon alfa-2a in HIV-1monoinfected participants: A phase II clinical trial', Journal of Infectious Diseases, vol. 201, no. 11, pp. 1686-1696. https://doi.org/10.1086/652420
Asmuth, David ; Murphy, Robert L. ; Rosenkranz, Susan L. ; Lertora, Juan J L ; Kottilil, Shyam ; Cramer, Yoninah ; Chan, Ellen S. ; Schooley, Robert T. ; Rinaldo, Charles R. ; Thielman, Nathan ; Li, Xiao Dong ; Wahl, Sharon M. ; Shore, Jessica ; Janik, Jennifer ; Lempicki, Richard A. ; Simpson, Yaa ; Pollard, Richard B. / Safely, tolerability, and mechanisms of antiretroviral activity of pegylated interferon alfa-2a in HIV-1monoinfected participants : A phase II clinical trial. In: Journal of Infectious Diseases. 2010 ; Vol. 201, No. 11. pp. 1686-1696.
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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 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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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

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

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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