Article

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

HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 10/2012; 207(2). DOI: 10.1093/infdis/jis663
Source: PubMed

ABSTRACT Background. Antiretroviral therapy (ART)-mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control HIV replication.Methods. 23 HIV-1 infected, virologically-suppressed subjects on ART (CD4 >450 cells/ml) were randomized to add Peg-IFN-α2A 180 (arm A) or 90 (arm B) μg/week to current ART. After 5 weeks, ART was interrupted and Peg-IFN-α2A continued for up to 12 weeks (primary endpoint) with option to continue to 24 weeks. Endpoints included virologic failure (viral load, VL ≥ 400 copies/ml) and adverse events. Residual VL and HIV-1 DNA integration were also assessed.Results. At week 12 of Peg-IFN-α2A monotherapy, viral suppression was observed in 9/20 (45%) subjects, a significantly greater proportion than expected (arm A p=0.0088; arm B p=0.0010; combined arms p<0.0001). Over 24 weeks, both arms had lower proportions of VL rebound than an historical control (arm A, p= 0.0046; arm B, p= 0.0011). Subjects who sustained VL < 400 copies/ml had decreased the levels of integrated HIV DNA (p= 0.0313), but increased residual VL (p=0.0078) when compared to subjects with endpoint failure.Conclusions. Peg-IFN-α2A immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immune-mediated approaches in HIV suppression and/or eradication.

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