Evolution of HIV-1 coreceptor usage during the progression of the disease. In most individuals HIV-1 infection is initially sustained by CCR5-using variants (R5, blue). In ~50% of the patients infected with subtype-B HIV-1, the CCR5-using variants acquire the ability to use CXCR4 (R5X4, blue/red) prior to AIDS diagnosis. Subsequently, these dual-tropic R5X4 variants may lose their ability to use CCR5 (X4 variants, red). Over time, viral coreceptor usage evolves resulting in viral variants with increased affinity for their respective coreceptor (increased color intensity).