Evaluation of the efficacy of hydroxychloroquine in decreasing immune activation and viral replication in asymptomatic HIV-infected patients . (360G-Wellcome-082163_Z_07_Z)

The proposal is to conduct a randomised, double-blind, placebo-controlled clinical trial of hydroxychloroquine for the treatment of early stage HIV infection. A total of 90 asymptomatic, antiretroviral na ve HIV-infected patients with CD4 T-cell counts greater than 400/ L and with no major contraindications to treatment will be recruited from major HIV treatment centres in or around London. Patients will be randomised to receive hydroxychloroquine 400mg/day or matching placebo to be taken once d aily by mouth for 48 weeks, and will be followed at regular (1 to 3 monthly) intervals for assessment of efficacy and safety. Efficacy parameters include measurement of T-cell activation, proliferation and apoptosis, viral load and absolute CD4 T-cell counts. Safety assessments include standard clinical and laboratory toxicity monitoring as well as rigorous observation for evidence of retinopathy. The primary endpoint is the change in CD8 T-cell activation at week 48 compared to baseline, and th e main secondary endpoints are change in viral load and CD4 T-cell count at week 48 compared to baseline (analysis will compare change in hydroxychloroquine and placebo groups). The study has 90% power to detect a 25% reduction in CD8 T-cell activation and a 0.4log reduction in viral load in the hydroxychloroquine group.