5th International AIDS Society Conference on HIV Pathogenesis and Treatment Cape Town - July 19 - 22, 2009

THE HLA CLASS II ALLELE DRB1*1303 IS ASSOCIATED WITH REDUCED VIRAL LOADS, INDEPENDENTLY OF HLAB57, IN AN HIV-1 CLADE C INFECTED AFRICAN POPULATION

IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOPDA104

B. Julg ^1,2, E. Moodley², K. Nair², M. van der Stok², K. Bishop², S. Reddy², Z. Mncube², Y. Qi³, P. Goulder^1,2,4, B. Walker^1,2,5, M. Carrington³, T. Ndung'u^2
1Ragon Institute of MGH, MIT and Harvard, Charlestown, United States, ²HIV Pathogenesis Program, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa, ³SAIC—Frederick, Inc., National Cancer Institute, Laboratory of Genomic Diversity, Frederick, United States, ⁴University of Oxford, Peter Medawar Building for Pathogen Research, Department of Pediatrics, Oxford, United Kingdom, ⁵Howard Hughes Medical Institute, Chevy Chase, United States

BACKGROUND: CD4+ T-cells are required for the development and maintenance of memory and cytotoxic CD8+ Tcells, however no clear association has been reported between histocompatibility complex class II alleles and control of HIV replication. We sought to investigate this potential association, analyzing MHC class II alleles, HIV-1 specific Tcell responses, and HIV disease progression in a cohort of 427 untreated HIV-1 clade C infected black South Africans.

METHODS: We performed HLA class I and II typing in a cohort of 427 antiretroviral naïve HIV-1 clade C infected Zulu/ Xhosa. Viral load was measured using the Roche Amplicor assay. CD4 cell counts and HIV-1 specific T-cell responses were measured by flow cytometry after stimulation with HIV peptide pools and staining for intracellular IFN-g secretion. Associations were tested using one-way ANOVA.

RESULTS: Individuals expressing the HLA DRB1*1303 allele (n=16, 4%) had significantly lower mean viral loads compared to subjects expressing other HLA class II alleles (mean log₁₀ VL: 3.93 vs 4.63, p=0.002). This effect remained significant, although weaker, after adjusting for HLA B57 (mean log₁₀ VL: 3.93 vs. 4.48; p<0.03). Surprisingly, reduced Gag specific CD4+ T-cells (p<0.01) were observed in individuals carrying DRB1*1303 whereas no difference in Gag specific CD8+ T-cell responses (p=0.42) was seen, suggesting that the protective effect of DRB1*1303 is not mediated by enhanced HIV-specific CD4+ T-cell responses or differences in the potency of induced HIV-specific CD8+ T-cell responses, at least in the peripheral circulation.

CONCLUSIONS: We demonstrate, for the first time, that the MHC class II allele DRB1*1303 is associated with lower viral load in a Zulu/Xhosa population in South Africa. This is independent of the protection conferred by HLA class I B57. However, this protective activity does not correlate with increased CD4+ T-cell functional responses, suggesting that DRB1*1303 may mediate its protective activity via an alternative mechanism.

2009-07-22
MOPDA104
Poster Discussion MOPDA1 - HLA Pathogen Interactions

Copyright © 2009 - International AIDS Society (IAS). All information and content relating to the abstracts from the 5th International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from the Elton John AIDS Foundation, National Library of Medicine, AIDS Walk of Orange County, and donations from users like you. Always watch for outdated information. This article first appeared in 2009. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2009. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.