AEGiS-15IAC: High frequency, broadly focused CTL activity is associated with low viraemia and high CD4 count in subjects expressing HLA-B57, B5801 or B5802 infected with HIV C Clade infection in Durban, South Africa.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

High frequency, broadly focused CTL activity is associated with low viraemia and high CD4 count in subjects expressing HLA-B57, B5801 or B5802 infected with HIV C Clade infection in Durban, South Africa.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10450)

Chetty P, Leslie A, Ramduth D, Addo MM, Altfeld M, Brander C, Brander C, Nene N, Ntumba N, Thobakgale C, Honeyborne I, Kiepiela P, Walker BD, Goulder PJ
HPP, Univ of Natal, Durban, South Africa

BACKGROUND: Cytotoxic T lymphocyte responses feature prominently in the HIV-specific immune response of all infected subjects, but some individuals progress rapidly to disease whilst in others progression is markedly slow. To examine the mechanisms underlying different rates of disease progression, we focused on 3 closely-related HLA class I molecules in a large cohort of HIV C clade infected subjects in Durban, South Africa. Two of the alleles, HLA-B57 and B5801, are associated with low viraemia in chronic infection, and the third, B5802, with high viraemia.

METHODS: Viral load, CD4 count and HLA type were determined in 545 chronically infected, HAART-naïve subjects. In 385 subjects CTL responses were analysed following peptide stimulation of PBMC using IFN-γ elispot and intracellular IFN-γ staining (ICS) assays. A panel of 410 overlapping peptides (OLPs) was used, whose synthesis was based upon the consensus C clade sequence.

RESULTS: HLA-B57 was independently associated with a low viral load (median: 8,497; p<0.0001, Mann Whitney), as was B5801 (median 14,400; p=0.009); B5802 was associated with a high viral load (median: 71,995; p<0.0001). Similarly, median CD4 counts were high in association with B57 or B5801 and low in B5802-positives. The number of OLPs targeted by B57-positive subjects (median 7, p=0.002) and B5801-positives (median: 8; p=0.001) was greater than in B5802-positives (median: 4). The magnitude of the HIV-specific CD8+ T cell response by ICS was greater in B57s (median 4.5%), and B5801s (3.4%) than B5802-positives (1.3%).

CONCLUSIONS: These data demonstrate that, for the alleles studied, high frequency, broadly focused CTL responses are associated with low viraemia and high CD4 count in chronic infection. This suggests that epitopes capable of being presented by all 3 closely related alleles represent useful CTL targets that result in effective control of HIV in the presence of the relevant CTL.

Keywords: AEGIS, CD4 Lymphocyte Count, HIV Infections, HLA-B Antigens, Viremia, Viral Load, HIV, T-Lymphocytes, Cytotoxic, HIV Seropositivity, CD8-Positive T-Lymphocytes, Acquired Immunodeficiency Syndrome, Disease Progression, HLA Antigens, Epitopes, HIV Antigens, HIV-1 Reverse Transcriptase, Alleles, South Africa, HLA-B57, immunology, genetics

040711
A10450