Effect of Interferon Alpha 2b Intensification on HIV-1 Residual Viremia in Individuals Suppressed on Antiretroviral Therapy

As a result of combination antiretroviral therapy (ART), morbidity and mortality from acquired immunodeficiency syndrome has declined significantly in the past 15 years, at least in developed countries. Human immunodeficiency virus type 1 (HIV-1) infected individuals now live longer, but must undergo continuous therapy that has substantial consequences on quality of life.

ART suppresses HIV-1 viremia below the limits of detection in current commercial assays (c. 50 copies/mL plasma), but HIV viremia persists even after prolonged suppressive therapy. The origin of this residual viremia is yet not clear, but data suggest that production from long lived HIV infected cells may contribute to viremia.

Antiretrovirals are extremely active against replicating cells, and can thus successfully stop viral replication, but have no effect on long-lived viral reservoirs of cells already infected with HIV-1 at the time antiretroviral therapy is initiated. As a result, new strategies are necessary to reduce or eradicate long-lived reservoirs.

Interferon alpha is a natural cytokine with antiviral activity. Prior to the introduction of antiretroviral therapy, several studies demonstrated modest effect of interferon alpha in HIV-1 viremia in active cycles of infection in infected individuals. Interferon alpha was also effective in vitro in decreasing virus production from cells chronically infected with HIV-1. With the introduction of potent antiretroviral therapy, interferon was not developed as a direct anti-HIV drug. Interferon alpha is relatively effective in therapy of hepatitis C virus (HCV) infection, and has been used in HIV-1/HCV coinfected individuals. Kottilil and coworkers in the Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases (NIAID) have shown a decrease in HIV-1 ribonucleic acid (RNA) levels in HCV coinfected participants treated with pegylated interferon alpha and ribavirin. In stored samples from that study, we conducted a retrospective trial on samples from participants with HIV-1 RNA levels of <50 copies/mL, showing a further reduction in residual viremia using an ultrasensitive Single Copy Assay (SCA) developed in our laboratory. As such the effects of interferon on HIV viremia and cell associated HIV RNA are of growing interest.

In this protocol we will conduct a prospective, non-randomized, single arm, pilot study to investigate the effect of pegylated interferon alpha 2b on HIV-1 RNA levels as an additional drug in participants undergoing suppressive antiretroviral therapy with viral RNA levels suppressed to less than 50 copies/mL plasma. As patients may have levels of HIV RNA that are lower than our limit of detection, we will also investigate levels of HIV nucleic acid species in cells as well. We will determine whether interferon alpha therapy will reduce residual viremia or cell associated HIV RNA in participants on suppressive ART, which will expand our understanding of persistent low-level viremia and the pathogenesis of HIV in infected individuals.