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Curr Opin HIV AIDS. 2009 Mar;4(2):118-24. doi: 10.1097/COH.0b013e3283223d46.

A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitors.

Author information

1
Weill Medical College of Cornell University, New York, NY 10065, USA. jpm2003@med.cornell.edu

Abstract

PURPOSE OF REVIEW:

Small molecule inhibitors targeting the CCR5 coreceptor represent a new class of drugs for treating HIV-1 infection. Maraviroc has received regulatory approvals, and vicriviroc is in phase 3 trials. Understanding how resistance to these drugs develops and is diagnosed is essential to guide clinical practice. We review what has been learned from in-vitro resistance studies, and how this relates to what is being seen, or can be anticipated, in clinical studies.

RECENT FINDINGS:

The principal resistance pathway in vitro involves continued use of CCR5 in an inhibitor-insensitive manner; the resistant viruses recognize the inhibitor-CCR5 complex, as well as free CCR5. Switching to use the CXCR4 coreceptor is rare. The principal genetic pathway involves accumulating 2-4 sequence changes in the gp120 V3 region, but a non-V3 pathway is also known. The limited information available from clinical studies suggests that a similar escape process is followed in vivo. However, the most common change associated with virologic failure involves expansion of pre-existing, CXCR4-using viruses that are insensitive to CCR5 inhibitors.

SUMMARY:

HIV-1 escapes small molecule CCR5 inhibitors by continuing to use CCR5 in an inhibitor-insensitive manner, or evades them by expanding naturally insensitive, CXCR4-using variants.

PMID:
19339950
PMCID:
PMC2896203
DOI:
10.1097/COH.0b013e3283223d46
[Indexed for MEDLINE]
Free PMC Article

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