Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration.
Enviado por Luis Montaner el
Título | Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Autores | Azzoni, L, Foulkes, AS, Papasavvas, E, Mexas, AM, Lynn, KM, Mounzer, K, Tebas, P, Jacobson, JM, Frank, I, Busch, MP, Deeks, SG, Carrington, M, O'Doherty, U, Kostman, J, Montaner, LJ |
Journal | J Infect Dis |
Volume | 207 |
Issue | 2 |
Pagination | 213-22 |
Date Published | 2013 Jan 15 |
ISSN | 1537-6613 |
Palabras clave | Adult, Antiviral Agents, Female, HIV Infections, HIV-1, Humans, Immunotherapy, Interferon-alpha, Male, Middle Aged, Polyethylene Glycols, Recombinant Proteins, Treatment Outcome, Virus Integration, Virus Replication |
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. |
DOI | 10.1093/infdis/jis663 |
Alternate Journal | J. Infect. Dis. |
PubMed ID | 23105144 |
PubMed Central ID | PMC3532820 |
Grant List | K02 AI078766 / AI / NIAID NIH HHS / United States K08AI073102 / AI / NIAID NIH HHS / United States K24 AI069994 / AI / NIAID NIH HHS / United States P30 AI 045008 / AI / NIAID NIH HHS / United States P30 CA10815 / CA / NCI NIH HHS / United States R21 AI087461 / AI / NIAID NIH HHS / United States U01AI065279 / AI / NIAID NIH HHS / United States |