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AIDS. 2017 Jan 14;31(2):191-197. doi: 10.1097/QAD.0000000000001298.

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

Author information

  • 1aDivision of Medical Virology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and National Health Laboratory Services bCentre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa cDepartment of Biomedical Laboratory Sciences, College of Medicine and Health Sciences, University of Rwanda, Butare, Rwanda dDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and National Health Laboratory Services, South Africa.

Abstract

OBJECTIVE:

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.

METHODS:

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/μl or 5 years postinfection. The gag gene was sequenced and HLA-associated changes between enrolment and 12 months postinfection were mapped.

RESULTS:

HLA-associated escape mutations were identified in 48 (62%) of the participants and were associated with CD4 decline to less than 350 cells/μl (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.

CONCLUSION:

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.

PMID:
27755110
PMCID:
PMC5177455
[Available on 2018-01-14]
DOI:
10.1097/QAD.0000000000001298
[PubMed - in process]
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