175 HIV-1 Evolution in Primary Infection is Affected by Stochastic Followed by Selective Processes

Abstract

Viral evolution in primary HIV-1 subtype B infection was assessed in 11 HIV-1-infected men who have sex with men (MSM): four transmitter:seroconverter transmission pairs and three independent seroconverters. Four hundred and seventy five near full-length HIV-1 genome sequences were generated, including ∼10 genomes per specimen at 2-12 visits over the first year of infection in the seroconverters. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled in acute HIV-1 infection. When the transmitter was in chronic infection, the founder variant in the seroconverter was rare in the transmitter's blood specimen. Although viral diversity underwent a slight contraction over the first 20 to 40 days, mutational patterns indicative of rapid population expansion rather than selection dominated during the first five weeks of infection. Subsequently, selection dominated over the whole proteome. Mutants were detected in the first week and became consensus as early as day 21 post onset of symptoms of primary HIV infection. We found multiple indications of CTL escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with nearby, mutually exclusive mutations, indicating continuing evolution of escape mutants, possibly in adaptation to viral fitness constraints or to evolving variant-specific immune responses.