Background:  An understanding of the viral characteristics required for transmission to, and establishment in, a new host will likely help in developing strategies to prevent HIV infection. To date, reports have been inconsistent on the level of heterogeneity and the characteristics of viral strains transmitted during primary infection.

Methods:  We retrospectively studied the viral characteristics of the HIV-1 subtype B envelope gene (1.2 kb, V1 to V5 region) from 37 men who have sex with men (MSM) followed in the Multicenter AIDS Cohort Study (MACS, a U.S. cohort of MSM followed since 1984) who had detectable plasma HIV-1 RNA at their last study visit prior to seroconversion. We used phylogenetic methods to estimate viral diversity and divergence, and to identify dual infections. Co-receptor usage (CCR5 and CXCR4) was assessed using V3 loop genotypic algorithms. V1-V2 loop lengths and potential N-linked glycosylation sites (PNLGS) for each subject were correlated to phylogenetic parameters and disease outcome measures.

Results:  We found a significant level of viral diversity (median 0.86%, IQR 0.69 to 1.25%, max 5.6%), as well as variation in V1-V2 loop length and PNLGS, but no evidence of dual infection. The complexity and level of diversity was equal to or greater than that of previous studies in both women and men. Using V3 loop genotypic co-receptor prediction algorithms viral variants were nearly all R5-tropic. In contrast to earlier studies, we found no correlation between any early viral genetic/variant parameters (ie, diversity, divergence, V1-V2 loop length, PNLGS) and HIV disease outcome measures. However, the V1-V2 loop length and number of PNLGS appear to be increasing over the time of the epidemic.

Conclusions:  In HIV-1 subtype B infection in MSM, multiple envelope variants can be found during acute infection and prior to the establishment of antibody responses. These results demonstrate that early viral populations in MSM can be as diverse as those previously reported in other risk groups, such as those transmitted heterosexually. However, acquisition or early appearance of a complex population of viral variants does not appear to be associated with disease outcome. In contrast, our finding of increasing variable loop length and glycosylation over calendar time may suggest that virus neutralization resistance may be increasing over time of the epidemic. Strategies to prevent HIV transmission will likely have to take these factors into account.