Possession of HLA class II DRB1*1303 associates with reduced viral loads in chronic HIV-1 clade C and B infection.
BACKGROUND
The HLA class II molecules play a central role in the generation of human immunodeficiency virus (HIV)-specific CD4(+) T-helper cells, which are critical for the induction of cytotoxic CD8(+) T cell responses. However, little is known about the impact of HLA class II alleles on HIV disease progression.


METHODS
In this study we investigated the effect of HLA class II alleles on HIV disease outcome and HIV-specific T cell responses in a cohort of 426 antiretroviral therapy-naive, HIV-1 clade C-infected, predominantly female black South Africans.


RESULTS
The HLA class II allele DRB1*1303 was independently associated with lower plasma viral loads in this population (P = .02), an association that was confirmed in a second cohort of 1436 untreated, HIV-1 clade B-infected, male European Americans, suggesting that DRB1*1303-mediated protection is independent of ethnicity, sex, and viral clade. Interestingly, DRB1*1303 carriage was not associated with an increased frequency of interferon (IFN) γ-positive HIV-specific CD4(+) T cell responses.


CONCLUSIONS
These data demonstrate the independent effect of an HLA class II allele, DRB1*1303, on HIV disease progression, in the absence of increased IFN-γ-positive HIV-specific CD4(+) T cell frequencies, suggesting that the protective activity of DRB1*1303 may be mediated via an alternative mechanism.
HIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu Natal Research Institute for TB and HIV, University of KwaZulu Natal, Durban, South Africa.
Boris
B
Julg
Eshia S
ES
Moodley
Ying
Y
Qi
Danni
D
Ramduth
Shabashini
S
Reddy
Zenele
Z
Mncube
Xiaojiang
X
Gao
Philip J
PJ
Goulder
Roger
R
Detels
Thumbi
T
Ndung'u
Bruce D
BD
Walker
Mary
M
Carrington
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D013019:South Africa; D016896:Treatment Outcome; D019562:Viral Load
D016207:Cytokines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains
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