What causes resistance to chemokine receptor antagonists in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Although experience with maraviroc is limited, treatment failure due to resistance has been observed. Resistance appears to occur via one of two mechanisms. The first mechanism is most likely through amino acid substitutions in the V3 loop of gp120. Although the specific mutations associated with resistance have not yet been described, they appear to allow HIV binding to the coreceptor despite the presence of maraviroc.

The second mechanism is not acquired resistance but rather the inability of phenotypic tropism assays to detect small quantities of CXCR4 virus that may be present, leading to overgrowth of CXCR4 virus in the presence of maraviroc and loss of viral control. The development of an enhanced tropism assay with higher sensitivity should minimize the frequency of this occurrence. [97, 98]

Genotypic assays can also be used to predict CCR5 and CXCR4 co-receptor tropism by sequencing the gp120 V3 loop. These assays have shown good-to-excellent concordance with phenotypic assays. [99, 100]

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