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- W2077261034 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." @default.
- W2077261034 created "2016-06-24" @default.
- W2077261034 creator A5022966532 @default.
- W2077261034 creator A5058715015 @default.
- W2077261034 date "2009-03-01" @default.
- W2077261034 modified "2023-09-23" @default.
- W2077261034 title "A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitors" @default.
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- W2077261034 doi "https://doi.org/10.1097/coh.0b013e3283223d46" @default.
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