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Mixed HIV Coreceptor Use Associated With Lower CD4 Count

Patients who have been heavily treated with antiretroviral drugs have a high proportion of viral strains that can use two types of chemokine receptors to infect cells, according// to a study published in the February 15th edition of Clinical Infectious Diseases.

The researchers, led by Timothy J Wilkin of Weill-Cornell Medical College, New York, also found that people with HIV that can use both receptors (known as dual-tropic virus) had lower CD4 cell counts than people with virus that uses the CXCR4 receptor (the viral type associated with a higher risk of disease progression). The findings lend further weight to the need to test for coreceptor usage in patients who may be eligible to take the new chemokine receptor inhibitor, maraviroc, now in development.

HIV infects cells by first binding to the CD4 receptor and then one of two coreceptors, the chemokine receptors CCR5 and CXCR4. Usually, these receptors are the targets for substances that activate white blood cells in response to inflammation. HIV that can use CCR5 tends to predominate early in infection while the presence of virus that can use CXCR4, known as syncitium-inducing virus, has been linked with an increased risk of progression to AIDS and death.

Currently, new potential antiretroviral treatments are in clinical trials to block chemokine receptors in the hope of preventing HIV entry into cells. The study reported here was part of a trial of the CCR5 inhibitor vicriviroc in heavily treatment-experienced patients.

The investigators write, “With their novel mechanism of action, CCR5 inhibitors should have antiretroviral activity for HIV-1–infected patients with uncontrolled viremia and few other treatment options (e.g. patients with multidrug-resistant virus)”. However, they note, these compounds are most likely to be effective if the individual is infected with CCR5-using virus alone. So the team tested the viral strains from all participants screened
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