Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV ‐infected patients receiving antiretroviral therapy

Objectives Chloroquine ( CQ ), an anti‐inflammatory drug, inhibits T oll‐like receptor ( TLR ) signalling in plasmacytoid dendritic cells ( pDCs ) and may be beneficial for HIV ‐infected patients in whom immune activation persists despite effective antiretroviral therapy ( ART ). The effect of CQ on CD4 T ‐cell recovery and immune activation in immune nonresponding patients receiving successful ART was therefore studied. Methods Nineteen adults on ART with CD4 counts ≤350 cells/μL and undetectable viral load ( VL ) orally received CQ at 250 mg/day for 24 weeks. Side effects, CD4 and CD8 T ‐cell counts, VL , T ‐cell activation, pDC proportion and plasma inflammatory markers were assessed at baseline, at 24 weeks, and at 12 weeks after CQ discontinuation (clinicaltrial.org registration # NCT02004314 ). Results CQ was well tolerated and all patients maintained an undetectable VL . The absolute CD4 and CD8 T ‐cell counts and their percentages, the pDC proportion, T ‐cell activation, D ‐dimer and C ‐reactive protein ( CRP ) plasma levels and the kynurenine/tryptophan ratio did not change with CQ treatment. Among nine cytokines/chemokines measured, only levels of interferon ( IFN )‐α2 were significantly increased by CQ treatment. Conclusions CQ was well tolerated in patients with low CD4 T ‐cell counts despite long‐term effective ART ; however, 24 weeks of CQ treatment did not improved CD4 T ‐cell recovery, lymphoid and myeloid immune activation or inflammatory markers.