The data reinforce the view that an interplay between positive (e.g., magnitude of persistent virus replication, evolutionary rate, change in target cell population) and negative (e.g., host immune response) selection forces that differ between individual hosts and at different stages of the infection course governs how R5 viruses respond to the changing environment and shape the frequency of expansion or switch to CXCR4 use. This evidence concerns the gene CXCR4 and infection.