Details

Autor(en) / Beteiligte

• Pereyra, Florencia
• Addo, Marylyn M.
• Kaufmann, Daniel E.
• Liu, Yang
• Miura, Toshiyuki
• Rathod, Almas
• Baker, Brett
• Trocha, Alicja
• Rosenberg, Rachel
• Mackey, Elizabeth
• Ueda, Peggy
• Lu, Zhigang
• Cohen, Daniel
• Wrin, Terri
• Petropoulos, Christos J.
• Rosenberg, Eric S.
• Walker, Bruce D.

Titel

Genetic and Immunologic Heterogeneity among Persons Who Control HIV Infection in the Absence of Therapy

Ist Teil von

• The Journal of infectious diseases, 2008-02, Vol.197 (4), p.563-571

Ort / Verlag

Chicago, IL: The University of Chicago Press

Erscheinungsjahr

2008

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Background. Spontaneous control of human immunodeficiency virus (HIV) infection has been documented in a minority of HIV-infected individuals. The mechanisms behind this outcome remain largely unknown, and a better understanding of them will likely influence future vaccine strategies. Methods. HIV-specific T cell and antibody responses as well as host genetics were examined in untreated HIVinfected patients who maintain comparatively low plasma HIV RNA levels (hereafter, controllers), including those with levels of < 50 RNA copies/mL (elite controllers, n = 64), those with levels of 50–2000 copies/mL (viremic controllers, n = 60); we also examined HIV-specific T cell and antibody responses as well as host genetics for patients with levels of >10,000 copies/mL (chronic progressors, n = 30). Results. CD8+T cells from both controller groups preferentially target Gag over other proteins in the context of diverse HLA class I alleles, whereas responses are more broadly distributed in persons with progressive infection. Elite controllers represent a distinct group of individuals who have significantly more CD4 and CD8 T cells that secrete interferon-γ and interleukin-2 and lower levels of HIV-neutralizing antibodies. Individual responses were quite heterogeneous, and none of the parameters evaluated was uniquely associated with the ability to control viremia. Conclusions. Elite controllers are a distinct group, even when compared to persons with low level viremia, but they exhibit marked genetic and immunologic heterogeneity. Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.