Resistance

Since maraviroc binds to the CCR5 co-receptor, there has been some concern that its use in patients with R5-tropic HIV might stimulate a shift to an HIV population that uses the alternative CXCR4 co-receptor. In addition to causing resistance to maraviroc, this may be linked to more rapid disease progression.

Overall, more treatment failures occurred in the MOTIVATE study, and occurred more quickly, in persons who developed shifts away from purely R5-tropic virus. At baseline, 751 maraviroc-treated patients had purely R5-tropic virus. Of these, 63 treatment failures occurred in people who had developed X4-tropic or dual/mixed virus, compared to 35 failures in people who still displayed only R5-tropic virus. Time to failure with an X4 or dual/mixed virus was approximately 30 days shorter than for failure with R5-tropic virus.

There was no association between CXCR4-using virus and category C events. Although it was not surprising that treatment failure would be associated with the emergence of X4- or dual-tropic virus, a less expected finding was that increases in CD4 cell counts were seen even if maraviroc treatment failed virologically.

Researchers also looked at whether viral tropism reverted to R5 in patients who had experienced a tropism shift and then stopped maraviroc treatment. In 14 patients who experienced a switch, the virus reverted to R5 tropism after a median of 16 days off maraviroc. Researchers concluded that this occurrence is consistent with selective and reversible suppression of CCR5-tropic viruses during maraviroc therapy, resulting in detection of dual/mixed or X4-tropic virus at time of failure in two-thirds of patients.¹

Maraviroc has no cross-resistance to drugs from other classes.