Home

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:
193
Metadata:
text | xml
Suggested Citation:
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, 2011, Virological and Immunological Factors Associated with HIV-1 Differential Disease Progression in HLA-B*58:01-Positive Individuals, Columbia University Academic Commons, http://hdl.handle.net/10022/AC:P:12497.

In Partnership with the Center for Digital Research and Scholarship at Columbia University Libraries/Information Services | Terms of Use