Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration
L Azzoni, AS Foulkes, E Papasavvas… - The Journal of …, 2013 - academic.oup.com
L Azzoni, AS Foulkes, E Papasavvas, AM Mexas, KM Lynn, K Mounzer, P Tebas…
The Journal of infectious diseases, 2013•academic.oup.comAbstract 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 …
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 …
Abstract
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.
Oxford University Press