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Longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection

Yager, Nicolea; Robinson, Nicolaa; Brown, Helena; Flanagan, Petera; Frater, Johna,b,c; Fidler, Sarahd; Weber, Jonathand; Phillips, Rodneya,b,c; the SPARTAC Trial Investigators

doi: 10.1097/QAD.0b013e32835b8cf5
Basic Science

Objective: To fully define cytotoxic T-lymphocyte (CTL) escape variants of an HLA-B*51-restricted integrase epitope in early HIV-1 infection.

Design: Ninety-four longitudinally sampled acute/early HIV-1 subtype B-infected participants were assessed to determine HLA-B*51-restricted LPPVVAKEI (LI9) escape variants.

Methods: LI9 was sequenced at baseline and subsequent time points. Interferon-γ (IFNγ) ELISpot assays were performed using serial log dilutions of variant LI9 peptides to determine the cellular response and functional avidity.

Results: There is a significant association between HLA-B*51 expression and an evolving LI9 sequence from baseline to year 1 (P < 0.0001). We detected that the V32I and P30X polymorphisms emerged within HLA-B*51+ participants over time. Reversion of the P30S polymorphism was observed by year 1 in one HLA-B*51 participant. LPPIIAKEI and LPSIVAKEI had significantly lower functional avidity compared with LPPVVAKEI and so may be less well recognized by LI9-specific CTLs; a positive IFNγ response to IPSVVAKEI was rarely seen. Functional avidity to wild-type LI9 inversely correlated with viral load (R2 = 0.448, P = 0.0485).

Conclusion: Our results provide support for the role of HLA-B*51-restricted CTLs and functional avidity in the control of early HIV-1 infection.

aNuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford

bThe James Martin 21st Century School, Peter Medawar Building for Pathogen Research

cOxford NIHR Biomedical Research Centre, Oxford

dDepartment of Medicine, Imperial College, London, UK.

Correspondence to Nicole Yager, Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK. E-mail: nicole.yager@stx.oxon.org

Received 3 May, 2012

Revised 7 October, 2012

Accepted 16 October, 2012

© 2013 Lippincott Williams & Wilkins, Inc.