Potential limitation of CCR5 antagonists: drug resistance more often linked to CXCR4-utilizing than to CCR5-utilizing HIV-1.
CCR5 antagonists are approved for treatment-experienced individuals, who are at risk of harboring both drug-resistant and CXCR4-utilizing (X4) HIV-1. If CXCR4 usage and drug resistance are linked, CCR5 antagonists may select for CXCR4-utilizing viruses resistant to antiretrovirals. Analysis of 117 individual viruses found that 69% of CXCR4-utilizing 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.
Wagner
Thor A
TA
University of Washington, Seattle, Washington, USA.
Frenkel
Lisa M
LM
D065100:CCR5 Receptor Antagonists; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D019713:Receptors, CCR5 / Q000627:therapeutic use*; D019718:Receptors, CXCR4 / Q000187:drug effects* / Q000235:genetics
D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5; D019718:Receptors, CXCR4