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Early evolution of human leucocyte antigen-associated escape mutations in variable Gag proteins predicts CD4+ decline in HIV-1 subtype C-infected women.


ABSTRACT: HIV-1 escape from cytotoxic T-lymphocytes results in the accumulation of human leucocyte antigen (HLA)-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of cytotoxic T-lymphocyte escape in a cohort followed from infection for 5 years.Viral loads and CD4 cell counts were monitored in 78 subtype C-infected individuals from onset of infection until CD4 cell count decline to less than 350 cells/?l or 5 years postinfection. The gag gene was sequenced and HLA-associated changes between enrolment and 12 months postinfection were mapped.HLA-associated escape mutations were identified in 48 (62%) of the participants and were associated with CD4 decline to less than 350?cells/?l (P?=?0.05). Escape mutations in variable Gag proteins (p17 and p7p6) had a greater impact on disease progression than escape in more conserved regions (p24) (P?=?0.03). The association between HLA-associated escape mutations and CD4 decline was independent of protective HLA allele (B57, B58?:?01 and B81) expression.The high frequency of escape contributed to rapid disease progression in this cohort. Although HLA-adaption in both conserved and variable Gag domains in the first year of infection was detrimental to long-term clinical outcome, escape in variable domains had greater impact.

SUBMITTER: Chopera DR 

PROVIDER: S-EPMC5177455 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Early evolution of human leucocyte antigen-associated escape mutations in variable Gag proteins predicts CD4+ decline in HIV-1 subtype C-infected women.

Chopera Denis R DR   Ntale Roman R   Ndabambi Nonkululeko N   Garrett Nigel N   Gray Clive M CM   Matten David D   Abdool Karim Quarraisha Q   Abdool Karim Salim S   Williamson Carolyn C  

AIDS (London, England) 20170101 2


<h4>Objective</h4>HIV-1 escape from cytotoxic T-lymphocytes results in the accumulation of human leucocyte antigen (HLA)-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of cytotoxic T-lymphocyte escape in a cohort followed from infection for 5 years.<h4>Methods</h4>Viral loads and CD4 cell counts were monitored in 78 subtype C-infected individuals from onset of infec  ...[more]

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