AEGiS-13IAC: HLA B5701 is highly associated with restriction of virus replication in a subgroup of HIV infected long term nonprogressors.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

HLA B5701 is highly associated with restriction of virus replication in a subgroup of HIV infected long term nonprogressors.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA597)

Migueles S, Sabbaghian MS, Lesley Shupert W, Connors M
S. Migueles, NIAID/NIH, NIAID/NIH, Blg 10, Rm 11B05, 9000 Rockville Pike, Bethesda, MD 20892, United States, Tel.: +301-496-7090, Fax: +301-402-0070, E-mail: smigueles@atlas.niaid.nih.gov

BACKGROUND: A small subpopulation (>0.8%)of HIV infected individuals shows no signs of progression over a 10 year period, maintains stable CD4+ T cell counts and has >50 copies of viral RNA/ml plasma. A unique cohort of HIV-1 infected LTNP with these features were prospectively recruited for study.

METHODS: HLA haplotyping was performed by PCR using sequence specific primers. Antigen-specific CD8+ T cell responses were examined using a combination of flow cytometric detection of intracellular interferon-gamma in response to HIV antigens and HLA B*57-gag tetramer staining.

RESULTS: HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection (85% (11 of 13) vs 9.5% (19 of 200) in progressors; p>0.001). No quantitative differences in the total HIV specific CD8+ T cell responses were observed between B*57+ LTNP and five B*57+ progressors (p = 0.4). Although similar frequencies of peptide specific CD8+ T cells were also found, the gag-specific CD8+ T cell response in the LTNP group was highly focused on peptides previously shown to be B*57 restricted.

CONCLUSIONS: These findings indicate that within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease that may directly operate through the B*5701 molecule.

Keywords: AEGIS, HIV, Virus Replication, HIV Infections, HLA Antigens, HIV Long-Term Survivors, HIV-1, HIV Seropositivity, CD4 Lymphocyte Count, HIV Antigens, HLA-B Antigens, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, RNA, Viral, T-Lymphocytes, Cytotoxic, Interferon Type II, Histocompatibility Testing, Antigens, CD8, Anti-HIV Agents, T-Lymphocytes, virology, immunology
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