Safety, Tolerability, and Mechanisms of Antiretroviral Activity of Pegylated Interferon Alfa-2a in HIV-1-Monoinfected Participants: A Phase II Clinical Trial

被引:102
作者
Asmuth, David M. [1 ]
Murphy, Robert L. [3 ]
Rosenkranz, Susan L. [4 ]
Lertora, Juan J. L. [5 ]
Kottilil, Shyam [5 ]
Cramer, Yoninah [4 ]
Chan, Ellen S. [4 ]
Schooley, Robert T. [2 ]
Rinaldo, Charles R. [7 ]
Thielman, Nathan [8 ]
Li, Xiao-Dong
Wahl, Sharon M. [5 ]
Shore, Jessica [3 ]
Janik, Jennifer [9 ]
Lempicki, Richard A. [6 ]
Simpson, Yaa [3 ]
Pollard, Richard B.
机构
[1] Univ Calif Davis, Med Ctr, Div Infect Dis, Sacramento, CA 95817 USA
[2] Univ Calif San Diego, San Diego, CA 92103 USA
[3] Northwestern Univ, Evanston, IL USA
[4] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[5] Natl Inst Hlth Clin Ctr, Bethesda, MD USA
[6] SAIC Frederick, Frederick, MD USA
[7] Univ Pittsburgh, Pittsburgh, PA USA
[8] Duke Univ, Durham, NC USA
[9] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA
关键词
CHRONIC HEPATITIS-C; IMMUNE-DEFICIENCY-SYNDROME; KAPOSIS-SARCOMA; IFN-ALPHA; PEGINTERFERON ALPHA-2A; HIV-1; INFECTION; PLUS RIBAVIRIN; COMBINATION THERAPY; REPLICATION CYCLE; VIRAL-INFECTIONS;
D O I
10.1086/652420
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 mu g 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 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/mu L (90% CI, -95 to 85 cells/mu L), 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.
引用
收藏
页码:1686 / 1696
页数:11
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