Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals.

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dc.creator Chopera, Denis.
dc.creator Mlotshwa, Mandla.
dc.creator Woodman, Zenda.
dc.creator Mlisana, Koleka.
dc.creator De Assis Rosa, Debra.
dc.creator Martin, Darren P.
dc.creator Abdool Karim, Salim Safurdeen.
dc.creator Gray, Clive M.
dc.creator Williamson, Carolyn.
dc.date.accessioned 2012-11-16T10:21:56Z
dc.date.available 2012-11-16T10:21:56Z
dc.date.created 2010
dc.date.issued 2010
dc.identifier.citation Chopera, D., et al. 2011. Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals. J. Virol. 85(14):7070-7080. en
dc.identifier.issn 0022-538X
dc.identifier.uri http://dx.doi.org/10.1128/JVI.02543-10. en
dc.identifier.uri http://hdl.handle.net/10413/7872
dc.description.abstract Molecular epidemiology studies have identified HLA-B*58:01 as a protective HIV allele. However, not all B*58:01-expressing persons exhibit slow HIV disease progression. We followed six HLA-B*58:01-positive, HIV subtype C-infected individuals for up to 31 months from the onset of infection and observed substantial variability in their clinical progression despite comparable total breadths of T cell responses. We therefore investigated additional immunological and virological factors that could explain their different disease trajectories. Cytotoxic T-lymphocyte (CTL) responses during acute infection predominantly targeted the TW10 and KF9 epitopes in p24Gag and Nef, respectively. Failure to target the TW10 epitope in one B*58:01-positive individual was associated with low CD4 counts and rapid disease progression. Among those targeting TW10, escape mutations arose within 2 to 15 weeks of infection. Rapid escape was associated with preexisting compensatory mutations in the transmitted viruses, which were present at a high frequency (69%) in the study population. At 1 year post infection, B*58:01-positive individuals who targeted and developed escape mutations in the TW10 epitope (n=5) retained significantly higher CD4 counts (P=0.04), but not lower viral loads, than non-B*58:01-positive individuals (n=17). The high population-level frequency of these compensatory mutations may be limiting the protective effect of the B*58:01 allele. en
dc.language.iso en en
dc.publisher American Society for Microbiology. en
dc.subject HIV infections--Immunology. en
dc.subject HIV infections--Virology. en
dc.title Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals. en
dc.type Peer reviewed journal article en

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