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

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.

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10.1086/652420

Publication Info

Asmuth, DM, RL Murphy, SL Rosenkranz, JJ Lertora, S Kottilil, Y Cramer, ES Chan, RT Schooley, et al. (2010). Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial. J Infect Dis, 201(11). pp. 1686–1696. 10.1086/652420 Retrieved from https://hdl.handle.net/10161/4148.

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Scholars@Duke

Thielman

Nathan Maclyn Thielman

Professor of Medicine

Broadly, my research focuses on a range of clinical and social issues that affect persons living with or at risk for HIV infection in resource-poor settings. In Tanzania, our group is applying novel methods to optimize HIV testing uptake among high-risk groups. We recently demonstrated that the Discrete Choice Experiment (DCE), a form of stated preference survey research, is a robust tool for identifying (a) which characteristics of HIV testing options are most preferred by different populations and (b) which tradeoffs individuals make in evaluating testing options. Building on more than a decade of productive HIV testing research in the Kilimanjaro Region, the next phase of our NIMH funded project will test the hypothesis that DCE-derived HIV testing options significantly increases rates of testing among groups at high risk for HIV infection. This work holds promise not only for optimizing HIV testing uptake in the Kilimanjaro Region, but also for applying novel tools in the service of translational epidemiology and implementation research.


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