Reduction of immune activation with chloroquine therapy during chronic HIV infection

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, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.

FIG. 1.

CD8 T-cell activation is decreased in HIV-infected individuals during chloroquine treatment. Percentages of CD38⁺ HLA-DR⁺ CD8 and CD4 memory T cells for chloroquine- (A and B) or placebo-treated (D and E) subjects are shown. Plasma viral RNA loads are also shown for chloroquine- (C) and placebo-treated (F) subjects. Each symbol, as indicated in Table 1, represents an individual study subject at day 0, month 1, or month 2 post-chloroquine or placebo treatment. n.d., not determined; CQ, chloroquine.

FIG. 2.

Ki-67 expression by CD8 and CD4 memory T cells is decreased in HIV-infected individuals during the first but not the second month of chloroquine treatment. The percentages of CD8 or CD4 memory T cells expressing Ki-67 for chloroquine- (A and B) or placebo-treated (C and D) subjects are shown. Each symbol is representative of each subject, as described in Table 1. n.d., not determined; CQ, chloroquine.

FIG. 3.

Plasma LPS levels in HIV-infected individuals are decreased during the first but not the second month of chloroquine treatment. Plasma LPS levels were determined as described in the text. P values were derived using the Wilcoxon matched-pairs test.