Hydrochloroquine study (HCQ)

Can hydroxychloroquine decrease immune activation in asymptomatic patients?

This study is now closed and results presented at the IAS conference in Rome in July 2011 showed that HCQ had no benefit and actually produced a slight drop in CD4 count. Study results link.

This MRC study is looking at whether an intervention in early asymptomatic infection may be able to reduce immune activation.

Early immune activation directly reduces CD4 cells and may also independently contribute to disease progression. Hydroxychloroquine (HCQ) is anti-malarial treatment first synthesised in 1955 that has other indications including systemic lupus erythematosus, cutaneous manifestations of dermatomyositis, hyperlipidaemias, thromboembolic prophylaxis in antiphospholipid antibody syndrome and rheumatoid arthritis.

Although the mechanism of action is unclear, by increasing endosomal pH, immune modulation is thought to interfere with steps in the T-cell activation pathway, including MHC class II antigen presentation and T-cell receptor mediated calcium signalling. Several studies have also indicated modest antiretroviral activity.

The tolerability profile was reported as being generally good, especially at low doses and when not used for chronic treatment, but grade 3/4 side effects include diarrhoea (in less than 10% patients) rash and headache (both in less than 5% patients), proximal muscle weakness (reversible) and retinopathy have been reported in less than 1% and 0.01% patients respectively.

This 48-week Phase II study will randomise 100 asymptomatic treatment-naïve patients (CD4 higher than 400 cells/mm3) to either 400mg HCQ (2 x 200mg tablets, once-daily) or matched placebo. In addition to standard monitoring a wide panel of immunological markers will be analysed.

The primary endpoint is change in activation of CD8+ T cells. Activation is estimated as 46% in untreated HIV, which drops to 11% in patients on HAART. This study is powered to detect reduction to 35% with HCQ which modelling suggests could decrease hazard of disease progression by over 50%.

Recruitment started in April 2008 and included 18 months follow-up.

This study is being run by the UK Medical Research Council (MRC).

Study information on MRC website

Study information on clinicaltrials.gov

Current status: Ongoing follow-up; closed to recruitment

For further details please contact: HCQ01@ctu.mrc.ac.uk