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

Denis R. Chopera; Mukelisiwe Mlotshwa; Zenda Woodman; Koleka P. Mlisana; Debra de Assis Rosa; Darren P. Martin; Salim Abdool Karim; Clive M. Gray; Carolyn Williamson

Title:
Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals
Author(s):
Chopera, Denis R.
Mlotshwa, Mukelisiwe
Woodman, Zenda
Mlisana, Koleka P.
Assis Rosa, Debra de
Martin, Darren P.
Abdool Karim, Salim
Gray, Clive M.
Williamson, Carolyn
Date:
Type:
Articles
Department:
Epidemiology
Volume:
85
Permanent URL:
Book/Journal Title:
Journal of Virology
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 postinfection, 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.
Subject(s):
Virology
Epidemiology
Publisher DOI:
10.1128/JVI.02543-10
Item views:
136
Metadata:
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