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13th International AIDS ConferenceDurban, South Africa - July 9-July 14, 2000 |
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA285)
Sinet M, Deschemin JC, Dupuis M, Dalod M, Chotard E, Meyer L, Deveau C, Delfraissy JF, Venet A
M. Sinet, Laboratoire Vni Faculte De Medicine, 63 Rue Gabriel Peri, Le Kremlin Bicetre 94276, France, Tel.: +33 1 49 596 719, Fax: +33 1 49 596 753, E-mail: martin.sinet@rb.u_psud.pg
BACKGROUND: To characterize the specific immune CD4+ and CD8+ T cell responses during primary HIV infection and to explore changes after treatment and their relationship to virological responses.
METHODS: T cell responses were evaluated in 24 subjects with primary HIV infection included in the French PRIMO cohort. After initiation of antiretroviral tritherapy, these responses were compared with changes in viral load over the subsequent 24 months. We used IFN-g ELISPOT assay and intracellular staining to characterize the ex vivo CD8+ T cell responses to a large variety of HIV epitopic peptides. Specific CD4+ T cell responses to HIV p24 antigen were examined by lymphoproliferative and IFN-g ELISPOT assays.
RESULTS: We observed HIV-specific CD8+ T cell responses in 71% of subjects. The number of peptides recognized was low (median 2, range 0-6). After 6 months of therapy, plasma HIV RNA was below 20 copies/mL in 60% of subjects and remained undetectable thereafter. In this case, the number of specific IFN-g producing cells decreased and no new peptide was recognized. At month 12, new specificities were observed only in patients with plasma HIV RNA > 1000 copies/mL. CD4+ T cell proliferative response to p24 protein was present in 36% of subjects at day 0. This response was correlated with the polyspecificity of the anti-HIV CD8+ T cell repertoire and negatively correlated with viral load. P24 proliferative response increased in the first months of treatment and was positve in 80% of subjects at month 6. This percentage decreased thereafter and no clear relationship with viral load was evidenced.
CONCLUSIONS: These results indicate that treatment during primary infection may increase antigen specific CD4+ T cell response. However, specific CD8+ T cell response is weak and does not increase in patients with controlled viral load. These results have potential importance for defining early therapeutic strategies of immunologic control of HIV replication.
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