Potential limitation of CCR5 antagonists: drug resistance more often linked to CXCR4-utilizing than to CCR5-utilizing HIV-1

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CCR5 antagonists are approved for treatment-experienced individuals, who are at risk of harboring both drug-resistant and CXCR4-utlizing (X4) HIV-1. If CXCR4 usage and drug resistance are linked, CCR5 antagonists may select for CXCR4-utlizing viruses resistant to antiretrovirals. Analysis of 117 individual viruses found that 69% of CXCR4-utlizing viruses versus 48% of R5 viruses had drug resistance mutations (P = 0.025). Linkage of X4 and drug resistance may limit the effectiveness of CCR5 antagonists.

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