Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4+ T cell depletion.

Carina L. Perez, Jeffrey M. Milush, Marcus Buggert, Emily M. Eriksson, Mette Voldby Larsen, Teri Liegler, Wendy Hartogensis, Peter Bacchetti, Ole Lund, Frederick M. Hecht, Douglas F. Nixon, Annika C. Karlsson

    Research output: Contribution to journalJournal articleResearchpeer-review

    279 Downloads (Pure)

    Abstract

    We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8+ T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francisco, were monitored from an estimated 44 days postinfection for up to 6 years. CD8+ T cells responses targeting HLA-matched HIV-Gag-epitopes were identified and characterized by multicolor flow cytometry. The autologous HIV gag sequences were obtained. We demonstrate that patients targeting a conserved HIV-Gag-epitope in early infection maintained their epitope-specific CD8+ T cell response throughout the study period. Patients targeting a variable epitope showed decreased immune responses over time, although there was no limitation of the functional profile, and they were likely to target additional variable epitopes. Maintained immune responses to conserved epitopes were associated with no or limited sequence evolution within the targeted epitope. Patients with immune responses targeting conserved epitopes had a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log10 difference). Furthermore, the rate of CD4+ T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a variable epitope (1.85% per month). Previous studies have shown that targeting of antigens based on specific HLA types is associated with a better disease course. In this study we show that categorizing epitopes based on their variability is associated with clinical outcome.
    Original languageEnglish
    JournalAIDS Research and Human Retroviruses
    Volume29
    Issue number3
    Pages (from-to)602-612
    ISSN0889-2229
    DOIs
    Publication statusPublished - 2013

    Cite this

    Perez, C. L., Milush, J. M., Buggert, M., Eriksson, E. M., Larsen, M. V., Liegler, T., Hartogensis, W., Bacchetti, P., Lund, O., Hecht, F. M., Nixon, D. F., & Karlsson, A. C. (2013). Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4+ T cell depletion. AIDS Research and Human Retroviruses, 29(3), 602-612. https://doi.org/10.1089/aid.2012.0171