Background:  During early infection neutralizing antibody responses to autologous virus drives successive waves of evolution in envelope. Virus neutralizing antibody escape is associated with changes in variable loop length, potential N-linked glycosylation sites (PNGS), and amino acid sequence. Here we characterize the viral envelope during the first 1 to 3 years post infection by measuring cell-to-cell fusogenicity, co-receptor tropism usage, and sensitivity to sCD4.

Methods:  Longitudinal samples from 38 untreated individuals with recent HIV-1 clade B infection were assessed for co-receptor tropism usage (Trofile assay), envelope-mediated cell to cell fusogenicity using an in-house assay, and autologous and heterologous neutralizing antibody and sensitivity to sCD4 utilizing a recombinant pseudovirus assay that evaluates the pool of envelopes present in the patient plasma.

Results:  Of the 38 early infection viruses, 35 were CCR5-utilizing (R5) throughout the first 3 years of infection; 1 was CCR5/CXCR4-tropic (dual/mixed) from the earliest time point; 1 virus switched tropism from dual/mixed to exclusively CXCR4-tropic during the first 6 months; and 1 switched from R5 to dual/mixed at 23 months post-infection. In 6 cases, the first sample had very high plasma viral RNA levels (6.0 to 7.7 log copies/mL), usually associated with acute viremia. Of these cases, 5 were characterized by high cell-cell fusion efficiency, and significantly increased sensitivity to sCD4 when compared with envelopes from samples with lower viral loads. Longitudinal isolates progressively lost fusogenicity and sCD4 sensitive as the viral load decreased.

Conclusions:  Early HIV infection is characterized by viruses that are predominantly CCR5 using, but utilization of CXCR4 is associated with increased viral loads. Envelopes from acute viremia viruses are more fusogenic and have greater sensitivity to sCD4. This result suggests that the viruses present early in infection are able to spread rapidly through efficient use of cellular CD4 and membrane fusion. This characteristic is lost quickly after the acute phase of infection, possibly due to the influence of the emerging neutralizing antibody response.