Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains

Human immunodeficiency virus (HIV) utilizes numerous mechanisms to evade the hosts immune response, including the selection of specific polymorphisms, termed viral adaptations, which can alter recognition and elimination by cytotoxic T-lymphocytes (CTLs). This study utilized three unique treatment-naive cohorts to characterize the initial CTL response to HIV, track the dynamics of viral adaptation during early infection, and examine how viral adaptations shape the circulating stains within one population over decades of time. Using an acute HIV-infected cohort, we applied genetic and cellular assays to identify evidence of anti-HIV CTL immune responses prior to antibody seroconversion providing an early selection environment. In the longitudinally-sampled chronic cohort, we identify viral adaptations already evident by the first year of infection that do not revert, and are stably retained over time. Finally, we present evidence for viral adaptations accumulating in the circulating strains of the Western Australian population over a thirty year period.