501-M. Disease Stage Does Not Influence the Frequencies of HIV-1-Specific Th1 Cells after Long-Term of Highly Efficient Antiretroviral Therapy

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Session 69 Poster Session
Immunopathogenesis Issues Addressed by Therapeutic Interventions
Session Time: 4:30-6:30 pm
Room 4E-F

501-M.

Disease Stage Does Not Influence the Frequencies of HIV-1-Specific Th1 Cells after Long-Term of Highly Efficient Antiretroviral Therapy
G. Carcelain*, N. Alatrakchi, A. Samri, R. Tubiana, C. Duvivier, S. Hilpert, V. Perrin, P. Debre, C. Katlama, and B. Autran
Hosp. Pitié-Salpétrière, Paris, France

Background: The aim of the study was to evaluate HIV-1-specific Th1-cell frequencies in large groups of patients treated for 1 to 3 years at different stages of the disease.
Methods: 79 HIV-1-infected patients (63 treated in chronic infection and 16 in primary infection [PI]) were enrolled in a study of CD4+ T-cell responses to HIV-1 p24 after 1 to 3 years of viral control (<200 copies/mL). CD4+ responses were analysed with a new IFN-gamma ELISPOT assay (threshold of positive responses was : 50 SFC/106 PBMC above background) and conventional T-cell proliferation assay.
Results: In ELISPOT assay, a CD4 response against HIV-1 can be detected in 56% of these 79 patients. No difference of frequency of responders to p24 is observed between patients treated in chronic infection and patients treated in PI with mean of positive responses of 56% and 81%, respectively. However, the mean frequency of HIV-1-specific Th1 cells is globaly very low (132+303 SFC/106 PBMC) although with wide ranges (0-1900 SFC/106 PBMC). Once again, no difference is observed whatever the stage of treatment initiation with a mean of 132+303 SFC/106 PBMC for patients treated at chronic stage and of 184+157 for patients treated at PI. We finally analysed the CD4+ HIV-1-specific responses in a sub-group of 11 immuno-suppressed patients with CD4 counts < 350/mm³ at baseline of treatment. While no proliferative responses were detectable in these patients, we can detect in ELISPOT assay a high frequency of positive responses (65%) against HIV and a mean of SFC/106 PBMC of 179+251 (ranges: 0-1020). Effect of treatment on this Th1-specific response will be detailed.
Conclusions: IFN-gamma ELISPOT assay allows detection of HIV-1-specific Th1 positive responses in large groups of patients even when no proliferative response is detected. CD4+ HIV-1-specific T cells are similarly detected in chronically and in PI treated patients despite long-term treatment with highly efficient antiretroviral therapy. Such responses can even be detected with a similar frequency before initiation of treatment in patients with < 350 CD4/mm³.