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Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration
Journal article   Open access   Peer reviewed

Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration

Livio Azzoni, Andrea S. Foulkes, Emmanouil Papasavvas, Angela M. Mexas, Kenneth M. Lynn, Karam Mounzer, Pablo Tebas, Jeffrey M. Jacobson, Ian Frank, Michael P. Busch, …
The Journal of infectious diseases, v 207(2), pp 213-222
26 Oct 2012
PMID: 23105144
url
https://academic.oup.com/jid/article-pdf/207/2/213/16866451/jis663.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1093/infdis/jis663View
Published, Version of Record (VoR) Open

Abstract

HIV-1 immunotherapy interferon-alpha Major and Brief Reports viral integration
Background.  Antiretroviral therapy (ART)–mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication. Methods.  A total of 23 HIV type 1 (HIV-1)–infected, virologically suppressed subjects receiving ART (CD4 + T-cell count, >450 cells/μL) were randomly assigned to have 180 μg/week (for arm A) or 90 μg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg–interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed. Results.  At week 12 of Peg–interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P < .0001). Over 24 weeks, both arms had lower proportions of subjects who had viral load, compared with the proportion of subjects in a historical control group (arm A, P = .0046; arm B, P = .0011). Subjects who had a sustained viral load of <400 copies/mL had decreased levels of integrated HIV DNA ( P = .0313) but increased residual viral loads ( P = .0078), compared with subjects who experienced end-point failure. Conclusions.  Peg–interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication. Clinical Trials Registration.  NCT00594880.

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Collaboration types
Industry collaboration
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Web of Science research areas
Immunology
Infectious Diseases
Microbiology
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