Clinical studies with chemokine receptor-5 (CCR5)-inhibitors

Boesecke, Christopha; Pett, Sarah L.b,c

doi: 10.1097/COH.0b013e328356e933
VIRAL TROPISM: Edited by Annemarie M.J. Wensing and Rolf Kaiser

Purpose of review: To summarise recently published clinical studies of chemokine receptor-5 (CCR5)-blockers, including the small-molecule blocker, maraviroc (MVC) and CCR5-monoclonal antibodies for HIV. MVC may have immunomodulating properties through CCR5-blockade. MVC appears well tolerated and penetrates the central nervous system. For these reasons, MVC is being investigated in immunodiscordance, prevention of IRIS and in HCV-HIV co-infection. Novel techniques allow tropism assignment via sequencing of proviral DNA; this testing platform is being utilised in MVC switch studies in those with HIV viraemia below the level of quantification. MVC is being utilised in regimen intensification studies for HIV associated neurocognitive disease.

Recent findings: MVC has no anti-inflammatory activity in rheumatoid arthritis. MVC appears well tolerated in hepatitis virus co-infected patients and MVC-intensification in HCV–HIV co-infection suggests a favourable impact on liver fibrosis. Early pilot data suggests MVC intensification may have functional benefit in the CNS. There is a growing body of data on tropism testing using proviral DNA; this technology is being utilised in MVC switch studies. CCR5-monoclonal antibodies administered subcutaneously are promising in Phase II development.

Summary: The place of MVC as an anti-HIV drug in the switch setting and as an immunomodulator is yet to be fully determined.

aDepartment of Internal Medicine I, University of Bonn, Bonn, Germany

bThe Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, New South Wales

cImmunology, HIV and Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, Australia

Correspondence to Christoph Boesecke, Department of Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Tel: +49 228 287 16558; fax: +49 228 287 15034; e-mail: christoph.boesecke@ukb.uni-bonn.de

© 2012 Lippincott Williams & Wilkins, Inc.