AEGiS-11IAC: Prospective follow-up studies of HIV-specific cytotoxic T lymphocytes (CTL) in a French cohort of 150 patients: IMMUNOCO.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Prospective follow-up studies of HIV-specific cytotoxic T lymphocytes (CTL) in a French cohort of 150 patients: IMMUNOCO.

Int Conf AIDS 1996 Jul 7-12; 11:222 (abstract no. Tu.A.280)
Autran B, Gomard E, Riviere Y, Agut H, Bouley JM, Katlama C; The Immunologie Cellulaire, CERVI, URA CNRS, Paris, France. Fax: (331) 42 17 74 90.

OBJECTIVES: to evaluate the precursor and memory CTLs directed against conserved epitopes from HIV-1, their evolution with disease progression, in relationship to immune, virological and clinical parameters.

METHODS: 138 HIV-1 infected stage II-III patients with CD4 counts greater than 400 (group A:67 pts), 200-400 (group B:65pts), less than 200/mm3 (group C:11pts) enrolled in 1991, subdivided in progressors and non progressors on the CD4 counts evolution. HIV-specific CTL were studied once a year using standardized assays: in-vitro restimulation of CTL, EBV target cells + rec. vacc. virus for the whole and truncated env, gag, pol, nef, rev, tat and vif genes from the HIV-1-LAI sequences.

RESULTS: we observed: 1) a high conservation of the CTL epitopes with positivity for 1 HIV-1-LAI protein in 87% or for 3 proteins in 60% patients whatever the group; 2) a stability of the antigenic profile recognized by CTL at the lst year in the 3 groups: 70-80% CTL against gag, pol, 50%: env, 40-50%: nef, 5-20%: tat, rev, vif;3) a slow time course decrease of CTL in transversal and longitudinal studies of 60 individuals tested over 3 years, with 77%, 67% and 37% gag, pol responses in A non progressors. A progressors and B non progressors respectively (p is less than 0.001) but 4) a transient enhancement of CTL activity in B progressors below 200 CD4/mm3 with a mean gag, pol positivity in 70% cases (p is less than 0.001), followed by a decrease to 40% responses in group C, suggesting a relationship between viral load or anti-retroviral treatment and CTL activity that will be discussed.

CONCLUSION: results from IMMUNOCO cohort clearly show: 1) the stability of the CTL responses to conserved HIV antigens and 2) the capacity to restimulate precursors and memory CTL during progression of the disease even at advanced stages of the disease. This indicates a lack of deletion in the global CTL repertoire against HIV and opens perspectives for immune therapies.

Keywords: AEGIS, HIV, T-Lymphocytes, Cytotoxic, HIV-1, Viral Load, HIV Antigens, CD4 Lymphocyte Count, Follow-Up Studies, HIV Infections, HIV-1 Reverse Transcriptase, HIV Long-Term Survivors, HIV Seropositivity, Longitudinal Studies, Disease Progression, Human, ICA11

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