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 12 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 (50
copies/mL plasma). Although therapy is not immediately curative, previous studies were
optimistic, suggesting prolonged duration of suppressive therapy could result in eventual
viral eradication. More recent data suggest, however, that HIV-1 RNA persists even after
prolonged suppressive therapy. The origin of this residual viremia is yet not defined but
data from several sources, including our own, indicate that persistent viremia may be the
product of viral genome production from chronically infected long-lived reservoirs, and not
from new ongoing cycles of HIV-1 infection.
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 may be 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. Recently,
Kottilil and coworkers in the Laboratory of Immunoregulation NIAID have shown a decrease in
HIV-1 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
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. We will determine whether interferon alpha
therapy will reduce residual viremia in participants on suppressive ART, which will expand
our understanding of persistent low-level viremia in HIV-1 infected individuals.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
We will compare viral RNA levels in blood drawn before, during, and after intensification with interferon.
Frank Maldarelli, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|