Article abstract

Nature Medicine 13, 46 - 53 (2006)
Published online: 17 December 2006 | doi:10.1038/nm1520

CD8+ T-cell responses to different HIV proteins have discordant associations with viral load

Photini Kiepiela1, Kholiswa Ngumbela1, Christina Thobakgale1, Dhanwanthie Ramduth1, Isobella Honeyborne2, Eshia Moodley1, Shabashini Reddy1, Chantal de Pierres1, Zenele Mncube1, Nompumelelo Mkhwanazi1, Karen Bishop1, Mary van der Stok1, Kriebashnie Nair1, Nasreen Khan1, Hayley Crawford2, Rebecca Payne2, Alasdair Leslie2, Julia Prado2, Andrew Prendergast2, John Frater2, Noel McCarthy3, Christian Brander4, Gerald H Learn5, David Nickle5, Christine Rousseau5, Hoosen Coovadia1, James I Mullins5, David Heckerman6, Bruce D Walker1,4,7 & Philip Goulder1,2,4

Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8+ T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein–specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8+ T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.

  1. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban 4013, South Africa.
  2. Department of Paediatrics, Nuffield Department of Medicine, Peter Medawar Building, South Parks Road, Oxford OX1 3SY, UK.
  3. Department of Zoology, Peter Medawar Building, South Parks Road, Oxford OX1 3SY, UK.
  4. Partners AIDS Research Center, Massachusetts General Hospital, 13th Street, Building 149, Charlestown, Boston, Massachusetts 02129, USA.
  5. Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
  6. Miscrosoft Research, One Microsoft Way, Redmond 98052, Washington, USA.
  7. Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815, USA.

Correspondence to: Philip Goulder1,2,4 e-mail:


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