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Journal of Virology, January 2009, p. 470-478, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01678-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus-Specific Gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point{triangledown}

Clive M. Gray,1* Mandla Mlotshwa,1 Catherine Riou,1 Tiyani Mathebula,1 Debra de Assis Rosa,1 Tumelo Mashishi,1 Cathal Seoighe,3 Nobubelo Ngandu,3 Francois van Loggerenberg,2 Lynn Morris,1 Koleka Mlisana,2 Carolyn Williamson,3 Salim Abdool Karim,2 on behalf of the CAPRISA 002 Acute Infection Study Team

AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa,1 Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Nelson R. Mandela School of Medicine, Durban, South Africa,2 Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa3

Received 6 August 2008/ Accepted 14 October 2008

It is unknown whether patterns of human immunodeficiency virus (HIV)-specific T-cell responses during acute infection may influence the viral set point and the course of disease. We wished to establish whether the magnitude and breadth of HIV type 1 (HIV-1)-specific T-cell responses at 3 months postinfection were correlated with the viral-load set point at 12 months and hypothesized that the magnitude and breadth of HIV-specific T-cell responses during primary infection would predict the set point. Gamma interferon (IFN-{gamma}) enzyme-linked immunospot (ELISPOT) assay responses across the complete proteome were measured in 47 subtype C HIV-1-infected participants at a median of 12 weeks postinfection. When corrected for amino acid length and individuals responding to each region, the order of recognition was as follows: Nef > Gag > Pol > Rev > Vpr > Env > Vpu > Vif > Tat. Nef responses were significantly (P < 0.05) dominant, targeted six epitopic regions, and were unrelated to the course of viremia. There was no significant difference in the magnitude and breadth of responses for each protein region with disease progression, although there was a trend of increased breadth (mean, four to seven pools) in rapid progressors. Correlation of the magnitude and breadth of IFN-{gamma} responses with the viral set point at 12 months revealed almost zero association for each protein region. Taken together, these data demonstrate that the magnitude and breadth of IFN-{gamma} ELISPOT assay responses at 3 months postinfection are unrelated to the course of disease in the first year of infection and are not associated with, and have low predictive power for, the viral set point at 12 months.

* Corresponding author. Mailing address: National Institute for Communicable Diseases, Private Bag X4, Johannesburg 2131, South Africa. Phone: 27 11 386 6372. Fax: 27 11 555 0502. E-mail: cgray{at}nicd.ac.za

{triangledown} Published ahead of print on 22 October 2008.

Journal of Virology, January 2009, p. 470-478, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01678-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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