Purpose of review: To present recent information on the evolution of coreceptor use from CCR5 alone to CCR5 and CXCR4, the impact CCR5 inhibitors have on this process, and new insights into HIV-1 binding to CD4 and CCR5.
Recent findings: The findings that are summarized include resistance to CCR5 inhibitors, genotypic predictors of coreceptor use, the link between coreceptor use and cell tropism, and new data on CCR5 structure and function.
Summary: Resistance to CCR5 inhibitors is uncommon, and frequently involves selection of minor populations of R5X4 virus. Genotypic predictors of coreceptor use need to take into account the entire envelope sequence, not just V3. Genetic polymorphisms in humans that affect CCR5 or chemokines that bind CCR5 affect not only virus entry but also immune reconstitution.