Background: Low-level HIV viremia originating from virus reactivation in HIV reservoirs is often present in cART treated individuals and represents a persisting source of immune stimulation associated with sub-optimal recovery of CD4+ T cells. The HIV-1 Tat protein is released in the extracellular milieu and activates immune cells and latent HIV, leading to virus production and release. However, the relation of anti-Tat immunity with residual viremia, persistent immune activation and CD4+ T-cell dynamics has not yet been defined. Methods: Volunteers enrolled in a 3-year longitudinal observational study were stratified by residual viremia, Tat serostatus and frequency of anti-Tat cellular immune responses. The impact of anti-Tat immunity on low-level viremia, persistent immune activation and CD4+ T-cell recovery was investigated by test for partitions, longitudinal regression analysis for repeated measures and generalized estimating equations. Findings: Anti-Tat immunity is significantly associated with higher nadir CD4+ T-cell numbers, control of low-level viremia and long-lasting CD4+ T-cell recovery, but not with decreased immune activation. In adjusted analysis, the extent of CD4+ T-cell restoration reflects the interplay among Tat immunity, residual viremia and immunological determinants including CD8+ T cells and B cells. Anti-Env immunity was not related to CD4+ T-cell recovery. Interpretation: Therapeutic approaches aiming at reinforcing anti-Tat immunity should be investigated to improve immune reconstitution in people living with HIV on long-term cART. Trial registration: ISS OBS T-002 ClinicalTrials.gov identifier: NCT01024556 Funding: Italian Ministry of Health, special project on the Development of a vaccine against HIV based on the Tat protein and Ricerca Corrente 2019/2020.

Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART / Tripiciano, A.; Picconi, O.; Moretti, S.; Sgadari, C.; Cafaro, A.; Francavilla, V.; Arancio, A.; Paniccia, G.; Campagna, M.; Pavone-Cossut, M. R.; Sighinolfi, L.; Latini, A.; Mercurio, V. S.; Pietro, M. D.; Castelli, F.; Saracino, A.; Mussini, C.; Perri, G. D.; Galli, M.; Nozza, S.; Ensoli, F.; Monini, P.; Ensoli, B.. - In: EBIOMEDICINE. - ISSN 2352-3964. - 66:(2021), pp. 1-12. [10.1016/j.ebiom.2021.103306]

Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART

Mussini C.;
2021

Abstract

Background: Low-level HIV viremia originating from virus reactivation in HIV reservoirs is often present in cART treated individuals and represents a persisting source of immune stimulation associated with sub-optimal recovery of CD4+ T cells. The HIV-1 Tat protein is released in the extracellular milieu and activates immune cells and latent HIV, leading to virus production and release. However, the relation of anti-Tat immunity with residual viremia, persistent immune activation and CD4+ T-cell dynamics has not yet been defined. Methods: Volunteers enrolled in a 3-year longitudinal observational study were stratified by residual viremia, Tat serostatus and frequency of anti-Tat cellular immune responses. The impact of anti-Tat immunity on low-level viremia, persistent immune activation and CD4+ T-cell recovery was investigated by test for partitions, longitudinal regression analysis for repeated measures and generalized estimating equations. Findings: Anti-Tat immunity is significantly associated with higher nadir CD4+ T-cell numbers, control of low-level viremia and long-lasting CD4+ T-cell recovery, but not with decreased immune activation. In adjusted analysis, the extent of CD4+ T-cell restoration reflects the interplay among Tat immunity, residual viremia and immunological determinants including CD8+ T cells and B cells. Anti-Env immunity was not related to CD4+ T-cell recovery. Interpretation: Therapeutic approaches aiming at reinforcing anti-Tat immunity should be investigated to improve immune reconstitution in people living with HIV on long-term cART. Trial registration: ISS OBS T-002 ClinicalTrials.gov identifier: NCT01024556 Funding: Italian Ministry of Health, special project on the Development of a vaccine against HIV based on the Tat protein and Ricerca Corrente 2019/2020.
2021
66
1
12
Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART / Tripiciano, A.; Picconi, O.; Moretti, S.; Sgadari, C.; Cafaro, A.; Francavilla, V.; Arancio, A.; Paniccia, G.; Campagna, M.; Pavone-Cossut, M. R.; Sighinolfi, L.; Latini, A.; Mercurio, V. S.; Pietro, M. D.; Castelli, F.; Saracino, A.; Mussini, C.; Perri, G. D.; Galli, M.; Nozza, S.; Ensoli, F.; Monini, P.; Ensoli, B.. - In: EBIOMEDICINE. - ISSN 2352-3964. - 66:(2021), pp. 1-12. [10.1016/j.ebiom.2021.103306]
Tripiciano, A.; Picconi, O.; Moretti, S.; Sgadari, C.; Cafaro, A.; Francavilla, V.; Arancio, A.; Paniccia, G.; Campagna, M.; Pavone-Cossut, M. R.; Sighinolfi, L.; Latini, A.; Mercurio, V. S.; Pietro, M. D.; Castelli, F.; Saracino, A.; Mussini, C.; Perri, G. D.; Galli, M.; Nozza, S.; Ensoli, F.; Monini, P.; Ensoli, B.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1245128
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