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 Toll-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.

Successful implementation of a national HLA-B*5701 genetic testing service in Canada.

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) that is used in combination antiretroviral therapy in HIV-infected patients. It is currently recommended as a preferred or an alternative NRTI in antiretroviral-naïve patients. The major toxicity of abacavir is a hypersensitivity reaction (HSR), which occurs in approximately 5% of treated patients. There is a strong association between the human leukocyte antigen (HLA)-B*5701 allele and abacavir HSR, which has allowed for rapid acceptance of genetic screening for HLA-B*5701 in clinical use. Canadian clinicians working in hospital centers with HLA typing capacity opted to launch a pilot project in 2006 to offer the screening test as standard of care to HIV-infected patients. Currently, more than 11,000 HLA-B*5701 tests have been performed, among which 6.3% are positive. Continued efforts have been made to ensure that testing is available to all HIV-infected patients to widen the patients' therapeutic options. HLA-B*5701 screening shows clinical use and preliminary data suggest cost-effectiveness.