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dc.creatorChopera, Denis.
dc.creatorMlotshwa, Mandla.
dc.creatorWoodman, Zenda.
dc.creatorMlisana, Koleka.
dc.creatorDe Assis Rosa, Debra.
dc.creatorMartin, Darren P.
dc.creatorAbdool Karim, Salim Safurdeen.
dc.creatorGray, Clive M.
dc.creatorWilliamson, Carolyn.
dc.date.accessioned2012-11-16T10:21:56Z
dc.date.available2012-11-16T10:21:56Z
dc.date.created2010
dc.date.issued2010
dc.identifier.citationChopera, 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.issn0022-538X
dc.identifier.urihttp://dx.doi.org/10.1128/JVI.02543-10.en
dc.identifier.urihttp://hdl.handle.net/10413/7872
dc.description.abstractMolecular 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.isoenen
dc.publisherAmerican Society for Microbiology.en
dc.subjectHIV infections--Immunology.en
dc.subjectHIV infections--Virology.en
dc.titleVirological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals.en
dc.typePeer reviewed journal articleen


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