A mutation in the gene that encodes the chemokine receptor CCR5 increases the risk of developing symptomatic infection with West Nile virus (WNV), according to a new study in the Journal of Experimental Medicine. Ironically, the same mutation (a 32-bp deletion, CCR5Δ32) provides strong protection against infection with HIV, as CCR5 is a co-receptor for HIV cell entry. WNV infection is now endemic in many parts of the world, including much of the United States. Although most people infected with WNV remain asymptomatic, about 20% develop a flu-like illness and 1% develop severe nervous-system disease. The authors looked at two cohorts of US patients with symptomatic WNV infection and found that 4–5% of infected people were homozygous for CCR5Δ32, compared with less than 1% of the general population. This indicates that homozygous CCR5Δ32 is a strong genetic risk factor for symptomatic WNV infection. The authors had previously shown that the movement of white blood cells into the brain in CCR5−/− mice is defective, and it is thought that this chemotactic defect might also explain the human findings. CCR5 inhibitors have been mooted as promising therapeutic agents to combat HIV, and several of these drugs are being used in clinical trials. This study raises concerns about the safety of administering such inhibitors to people living in WNV endemic areas. JEM

A large international AIDS therapy trial has been halted by the US government because of concerns about the health of participants receiving intermittent antiretroviral therapy (ART). The Strategies for Management of Anti-Retroviral Therapy (SMART) trial was set up to compare the clinical benefit of two HIV treatment strategies — ongoing treatment with ART and episodic or 'stop–start' treatment. Patients receiving episodic ART treatment were given medication only when their CD4+ T cells dropped below a certain level and treatment was discontinued when the CD4+ T-cell count recovered. But a recent review by the trial's safety committee found that patients receiving episodic treatment were twice as likely to die or become ill compared with those receiving continual treatment. The failure of intermittent therapy for HIV comes as a disappointment. Although antiretroviral therapy is lifesaving, the cost of lifelong treatment has limited its use in many developing countries. The risk of virus resistance, as well as the severe side effects of many of the drugs, has also made shorter or intermittent treatment regimens an attractive option. BBC, NIH press release

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