Background: Superinfection with a second strain of HIV-1 has important implications for understanding HIV transmission and for vaccine development. However, the frequency and pathogenic consequences of superinfection are largely unknown, as are the underlying host-virus interactions associated with HIV-1 superinfection.

Methods: From the Multicenter AIDS Cohort Study (MACS), 32 seroconverters were retrospectively evaluated for HIV-1 superinfection using a combination of heteroduplex mobility assay (HMA), sequencing of the envelope C2-V5 region, and phylogenetic methods. HLA class II typing of samples was used to confirm superinfection. Subjects were also typed for HLA and CCR variants known to influence disease progression.  Outcome of HIV infection was measured using: time to clinically defined AIDS, time to CD4+ T-cell count <200/mL, and plasma RNA viral load. Phylogenetic and population genetic methods were used to analyze viral dynamics.

Results: HIV-1 superinfection was detected in 1 of 32 subjects.  Superinfection in this subject occurred with a second HIV-1 subtype B strain between 0.8 and 1.3 years post-seroconversion (SC). In this subject time from seroconversion to a CD4+ T-cell count <200/ul was 2.4 years and time from seroconversion to AIDS (PCP) was 3.4 years. There was rapid replacement of the initial virus by the superinfecting virus in plasma within 6 months, and no evidence of the initial strain in PBMC at 3.3 years post-SC. By population dynamic and phylogenetic analyses, random genetic drift could not completely explain replacement by the superinfecting virus. In addition, this subject’s HIV viral load, and pattern of HLA and CCR polymorphisms did not fully explain his rapid disease progression.

Conclusions: This is the first description of a case of HIV-1 superinfection in an individual with rapid progression to AIDS. Emergence of, and replacement by, the superinfecting virus appears to have occurred under selective pressure. It is not clear, however, whether superinfection leads directly to rapid progression, or whether certain hosts, who are intrinsically more likely to experience a rapid disease course, are also less likely to restrict new infections.

Keywords: Superinfection; Disease Progression; Evolution