Figure 1.

Potential mechanisms of resistance of HIV to CCR5 antagonists. HIV can become resistant to CCR5 inhibitors in a number of ways. The virus can adapt to scavenge low levels of unbound coreceptors more efficiently either by binding coreceptors with higher affinity or triggering fusion more quickly (1). HIV could also become resistant by competing off drug from coreceptors (2) or by using a drug-bound conformation of the coreceptor (3). Alternatively, the virus could switch to using CXCR4, either via a de novo switch or due to emergence of a pre-existing X4 virus (4), or it could switch to using an alternative coreceptor (5).