HIV entry: new insights and implications for patient management

Abstract

The discovery of the chemokine coreceptors CCR5 and CXCR4, essential for HIV entry, provoked over a decade of research into the mechanism of HIV entry and potential targets for treatment and prevention of HIV. This review article reports the recent published data regarding licensed and investigational HIV entry inhibitors including CCR5 and CXCR4 antagonists, fusion inhibitors and attachment inhibitors. The results from the maraviroc and vicriviroc clinical trials are reported, showing the efficacy and safety of CCR5 antagonists in treatment of multidrug resistant HIV. The poor sensitivity of the original screening tropism assay is associated with virological failure in individuals mislabelled R5 tropic who receive CCR5 antagonists. Reanalyses of clinical trials using a superior screening assay are in progress. Superior immunological restoration is seen with CCR5 antagonists that may be of benefit to individuals with discordant CD4 cell response with antiretroviral therapy and to those with severe immunosuppression. Research and development of HIV entry inhibitors is ongoing and provides new classes of drug that can be used in the treatment of HIV. Clinical trials will soon commence to assess the benefit of CCR5 antagonists in immune reconstitution and other therapeutic uses.