Mlotshwa, Mandla.Riou, Catherine.Chopera, Denis Rutendo.de Assis Rosa, Debra.Ntale, Roman.Treurnicht, Florette K.Woodman, Zenda.Werner, Lise.van Loggerenberg, Francois.Mlisana, Koleka Patience.Williamson, Carolyn.Gray, Clive M.Abdool Karim, Salim Safurdeen.2012-11-122012-11-1220102010Mlotshwa M., Riou C., Chopera D., et al. Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV-1 infection and associations with early disease progression. J Virol. 2010;84(22):12018–12029.0022-538Xhttp://dx.doi.org/10.1128/JVI.01472-10http://hdl.handle.net/10413/7835Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-y) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-y-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection.enHIV infections--Virology.HIV infections--Immunology.Peer reviewed journal article