AEGiS-14IAC: The magnitude of HIV-specific cytotoxic T lymphocyte responses is not negatively associated with viremia in c-clade infected South African Zulu adults.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

The magnitude of HIV-specific cytotoxic T lymphocyte responses is not negatively associated with viremia in c-clade infected South African Zulu adults.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10088)

Mngqundaniso N, Govender U, Ramduth D, Chetty P, Tang Y, Addo M, Altfeld M, Brander C, Coumi N, Walker B, Coovadia HM, Kiepiela P, Goulder P
University of Natal, NRMSM, Durban, South Africa

BACKGROUND: Analyses of B clade infected Caucasians have described a negative association between HIV Gag-specific cytotoxic T lymphocyte (CTL) numbers and the level of viraemia. Particular Gag-specific epitopes commonly targeted depend upon the HLA class I molecules prevalent in that population.

METHODS: Gag-specific CTL activity was quantified by using overlapping peptides spanning p24 Gag corresponding to the C clade consensus sequence. These pooled peptides were incubated with PBMC from study subjects and intracellular interferon-gamma producing cells analysed by flow cytometry. Responses of > 0.03% of CD8+ T cells above background were regarded as significant, with > 100,000 lymphocytes analysed in each subject. Background responses were defined as < 0.03% of CD8+ T cells analysed. CTL activity was also quantified by staining of PBMC using a peptide-MHC tetrameric complex specific for the dominant Gag-specific CTL response in subjects expressing either HLA-B42 or B81 (accounting for 31% of the study population).

RESULTS: The p24 Gag-specific CD4+ T cell response was evaluated in 152 C clade infected Zulu adults not receiving antiretroviral therapy, living in Durban, South Africa. Significant p24 Gag-specific CTL responses were detectable in 135/150 (90%) subjects (median: 0.59% of CD8+ T cells, range 0.03% - 11.0%). Tetramer responses in the B42/B81-positive subjects were in the range 0.03% - 2.0%.There was no significant association between HIV-specific CD8+ T cell numbers, measured by ICS or tetramer, and control of viraemia, or absolute CD4 T cell numbers or CD4 percentage of lymphocytes in the peripheral blood.

CONCLUSION: No negative association exists between HIV-specific CD8+ T cell acivity and control of HIV infection in C clade infected adult Zulu. Responses towards peptides based on autologous virus sequences and to viral proteins other than p24 Gag will be explored further.

Keywords: AEGIS, HIV, T-Lymphocytes, Cytotoxic, HIV Infections, Viremia, HIV Antigens, HIV Seropositivity, HIV Core Protein p24, African Continental Ancestry Group, Epitopes, Antigens, CD8, HLA Antigens, HIV Envelope Protein gp160, South Africa, Adult, immunology

020707
A10088