HIV subtype and Nef-mediated immune evasion function correlate with viral reservoir size in early-treated individuals

The HIV accessory protein Nef is genetically diverse and modulates key immune evasion and pathogenic functions. Recent early HIV-specific adaptive immune responses were identified as correlates of HIV reservoir size. So, we hypothesized that viral factors facilitating evasion of such responses might also influence reservoir establishment and/or persistence. Plasma HIV RNA-derived nef clones were isolated from 30 acute/early-infected individuals and assessed for their CD4 and HLA-I downregulation function in vitro. We explored the relationships between baseline clinical, immunologic and virologic characteristics, and HIV reservoir size measured 48 weeks following initiation of suppressive cART. Nef-mediated HLA downregulation correlated positively with reservoir size. Furthermore, this function was retained in final multivariable models adjusting for established clinical and immunologic correlates of reservoir size. HIV subtype B infection also emerged as a significant correlate of reservoir size on cART. Results highlight potentially important role of viral factors in modulating viral reservoir establishment and persistence.