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CTN 246: Chloroquine to reduce T cell immune activation in HIV-infected individuals

Chloroquine as a modulator of T cell immune activation to improve CD4 recovery in HIV-infected participants receiving antiretroviral therapy: A proof-of-concept study

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About the study

Up to 30% of individuals successfully treated with ART do not achieve a strong CD4 T cell recovery and therefore, remain at risk for AIDS and non-AIDS infections and diseases. Among factors associated with low CD4 T cell recovery is T cell activation, which stimulates Toll-like receptors (TLR). TLR play a crucial role in this innate immune response. Researchers hope that by blocking TLR engagement by chloroquine, an antimalarial medication, T cell immune activation would be reduced and in turn would promote CD4 recovery when HIV replication is suppressed by ART.

Study approach

The study recruited 19 HIV+ individuals with undetectable viral loads. Eligible participants received an oral dose of chloroquine (250 mg) once daily from week 8 through week 32. All participants were asked to have rectal biopsy samples (week 0 and week 32) to study T cell immune activation in the mucosa rectal site. Side effects, CD4 and CD8 T-cell counts, viral load, T-cell activation, and plasma inflammatory markers were assessed at baseline, at 24 weeks, and at 12 weeks after chloroquine discontinuation.

Results

Investigators found that chloroquine was well-tolerated and all patients maintained an undetectable VL. The overall conclusion was that chloroquine is well tolerated in patients with low CD4 T-cell counts, despite long-term effective ART; however, 24 weeks of chloroquine treatment did not improve CD4 T-cell recovery, lymphoid and myeloid immune activation, or inflammatory markers.

Publication 

Routy JP, Angel JB, Patel M, Kanagaratham C, Radzioch D, Kema I, Gilmore N, Ancuta P, Singer J, Jenabian MA. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy. HIV Med. 2015 Jan;16(1):48–56.

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