AEGiS-14IAC: HIV-specific cytotoxic T cell responses persist in the lymphoid tissue during HAART in chronic HIV infection and redistribute after treatment interruption.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

HIV-specific cytotoxic T cell responses persist in the lymphoid tissue during HAART in chronic HIV infection and redistribute after treatment interruption.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1180)

van Lunzen J, Altfeld M, Frahm N, Stellbrink HJ, Walker BD
University Hospital Eppendorf, Hamburg, Germany

BACKGROUND: To characterise HIV-specific immune responses in peripheral blood (PB) and lymph nodes (LN) after long-term control of viral replication.

METHODS: HIV-specific CD8+ T cell responses (CTL) were assessed simultaneously in LN and PB by ELISpot, ICS and tetramers in patients receiving successful HAART for prolonged periods of time. Results were correlated to virological set point levels, distribution of T cells and parameters of immune activation.

RESULTS: 15 chronically infected patients with VL <25 c/ml for a median of 13 months during HAART were selected. Patients underwent a LN biopsy and lumbar puncture after 12 mths. of HAART showing no or minimal residual viral replication in LN and CSF followed by a single supervised treatment interruption (STI). All patients experienced a rebound of peripheral VL to pre-treatment levels (450,000 c/ml at BL vs. 230,000 c/ml during STI, p=0.54) within 2 to 6 weeks after STI which was associated with a rapid re-expression of activation markers on T cells (CD69, CD38, HLA-DR) and increase in T cell proliferation (Ki-67). This resulted in a re-inversion of the previously normalised CD4/CD8 ratio. The kinetics of viral rebound and increase in cycling CD8+Ki-67+ T cells was strongly correlated. Further characterization of HIV-specific CTL responses showed that initially the magnitude of epitope-specific CD8+ T cell activity was significantly higher in LN than in PB (p<0.01). Responses decreased in both compartments during HAART, but this decline was more pronounced in PB. After STI HIV-specific CTL reappeared in PB, however, enhancement in breadth and magnitude was due to the expansion of pre-existing CTL responses in LN with new epitopes infrequently targeted.

CONCLUSIONS: Prolonged periods of successful HAART fail to induce novel HIV-specific CTL responses in chronic HIV infection. The increase in CTL frequencies during STI is most likely the result of the expansion of pre-existing clones from LN.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV Infections, T-Lymphocytes, Cytotoxic, Acquired Immunodeficiency Syndrome, CD8-Positive T-Lymphocytes, Lymphoid Tissue, Virus Replication, HIV Seropositivity, Epitopes, Human, virology, immunology

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TuOrA1180