Clade BHIV-1 superinfection with wild-type virus after primary infection with drug-resistant clade B virus

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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. (C) 2003 Lippincott Williams Wilkins.