A newly published analysis of a small, 8-week study of the
antimalarial drug chloroquine reports a significant decline in CD8 T cell
activation (as measured by expression of CD38 and HLA-DR) and CD8 and CD4 T
cell turnover (measured by the cell cycle marker Ki67). A slightly larger
30-person study involving 12 weeks of chloroquine treatment is now being conducted by the ACTG. Both studies involve people not
receiving antiretroviral therapy (ART). Given that there is an association
between persistent immune activation and poor immune reconstitution on ART,
these results suggest chloroquine may also deserve evaluation in immunological
non-responders who currently have few
research options. In terms of the mechanism of action, the authors of the new
paper note that chloroquine is known to inhibit signaling via several immune
system proteins called toll-like receptors (TLR3, TLR7, TLR8, and TLR9) and
they state that “it is plausible that suppression of intracellular TLR
signaling resulted in the decrease in CD38+ HLA–DR+ CD8 T cells.”
J. Virol. doi:10.1128/JVI.01466-10
Reduction of Immune Activation during Chronic HIV Infection
with Chloroquine Therapy
Shannon M Murray, Carrie M Down, David R Boulware, William M
Stauffer, Winston P Cavert, Timothy W Schacker, Jason M Brenchley, and Daniel C
Douek
National Institutes of Health, National Institute of Allergy
and Infectious Diseases, Vaccine Research Center, Human Immunology Section,
Bethesda, MD; Division of Infectious Diseases and International Medicine, Dept.
of Medicine, University of Minnesota, Minneapolis, MN
Abstract
Increased levels of activated T cells are a hallmark of the
chronic stage of human immunodeficiency virus (HIV) infection and are highly
correlated with HIV disease progression. We evaluated chloroquine (CQ) as a
potential therapy to reduce immune activation during HIV infection. We found
that the frequency of CD38+ HLA-DR+ CD8 T cells, as well as Ki-67 expression in
CD8 and CD4 T cells, were significantly reduced during CQ treatment. Our data
indicate that treatment with CQ reduces systemic T cell immune activation and
thus its use may be beneficial for certain groups of HIV-infected individuals.
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