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The immunological response to HIV-1 infection has been postulated to impede superinfection with a second virus; however, a few recent reports have documented cases of HIV-1 superinfection in humans either from different viral clades or from the same clade.To differentiate between co-infection and superinfection in a patient harboring a distinct wild-type HIV 4 months after primary infection with drug-resistant HIV.Detailed dye primer and clonal sequencing along with length polymorphism analysis was used to investigate the evolutionary linkage between viral populations sampled at different timepoints.After a set point viral load of −6000 copies HIV RNA/ml, the viral load jumped to 34 000 copies/ml at month 4 and, shortly after, to almost 200 000 copies/ml. At that time a second viral strain was first detected by dye primer sequencing of a pol fragment. These findings were confirmed by analysis of a 1300 bp gag–pol fragment and clonal sequencing and phylogenetic analysis of the V3 region. Length polymorphism analysis of the gp120 V4–V5 region showed that the second viral population was absent even as a minority population until month 4, when it was found to be the majority population, and the initial variant was present only as a minority. Both strains were subtype B.These data support intraclade HIV-1 superinfection by wild-type virus in the absence of antiretroviral therapy in a patient initially infected with drug-resistant HIV. The substantially different in-vivo viral growth characteristics observed illustrate the potential for superinfection to impact disease progression.