Here, we characterized the ability of luciferase reporter viruses pseudotyped with HIV-1 Envs (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naïve subjects experiencing progression from chronic to advanced C-HIV infection over an approximately 3-year period, who either exclusively maintained CCR5-using (R5) variants (n = 20 subjects) or who experienced a coreceptor switch to CXCR4-using (X4) variants (n = 1 subject), to utilize alternative coreceptors for entry. This evidence concerns the gene CCR5 and HIV infectious disease.