Safety, Immune, and Antiviral Effects of Pegylated Interferon Alpha 2b Administration in Antiretroviral Therapy-Suppressed Individuals: Results of Pilot Clinical Trial

Emmanouil Papasavvas, Livio Azzoni, Amélie Pagliuzza, Mohamed Abdel-Mohsen, Brian N. Ross, Matthew Fair, Bonnie J. Howell, Daria J. Hazuda, Nicolas Chomont, Qingsheng Li, Karam Mounzer, Jay R. Kostman, Pablo Tebas, Luis J. Montaner

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In the pilot NCT01935089 trial, we tested whether pegylated interferon alpha2b (Peg-IFN-α2b) with antiretroviral therapy (ART) was safe and could impact HIV and immune measures in blood and in gut-associated lymphoid tissue (GALT). Twenty HIV-1+ ART-suppressed individuals received 1 μg/kg/week Peg-IFN-α2b with ART for 20 weeks, with intermediate 4-week analytical ART interruption (ATI). Safety, immune activation, HIV viral load and integrated HIV DNA in blood, and HIV RNA and DNA in gut biopsies were measured. A total of 7/20 participants experienced grade 3-4 adverse events, while 17/20 participants completed the study. Of the 17 participants who completed the study, 8 remained suppressed during ATI, while all 17 were suppressed at end of treatment (EoT). As expected, treatment increased activation of T and natural killer (NK) cells and IFN-stimulated molecule expression on monocytes in periphery. While circulating CD4+ T cells showed a trend for a decrease in integrated HIV DNA, GALT showed a significant decrease in HIV-1 RNA+ cells as measured by in situ hybridization along with a reduction in total HIV DNA and cell-associated RNA by EoT. The observed decrease in HIV-1 RNA+ cells in GALT was positively associated with the decrease in activated NK cells and macrophages. This study documents for the first time that 20 weeks of immunotherapy with Peg-IFN-α2b+ART (inclusive of a 4-week ATI) is safe and results in an increase in blood and GALT immune activation and in a significant decrease in HIV-1 RNA+ cells in GALT in association with changes in innate cell activation.

Original languageEnglish (US)
Pages (from-to)433-443
Number of pages11
JournalAIDS Research and Human Retroviruses
Volume37
Issue number6
DOIs
StatePublished - Jun 2021
Externally publishedYes

Keywords

  • GALT
  • HIV DNA
  • HIV RNA
  • activation
  • antiretroviral therapy
  • pegylated IFN-α2b

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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