Anti-Tat immunity defines CD4+ T-cell dynamics in people living with HIV on long-term cART
| Autor: | Giovanni Di Perri, Giovanni Paniccia, Cecilia Sgadari, Barbara Ensoli, Laura Sighinolfi, Sonia Moretti, Paolo Monini, Annalisa Saracino, Maria Rosaria Pavone-Cossut, Vito S. Mercurio, Massimo Di Pietro, Alessandra Latini, Orietta Picconi, Francesco Castelli, Fabrizio Ensoli, Angela Arancio, Vittorio Francavilla, Silvia Nozza, Aurelio Cafaro, Massimo Galli, Massimo Campagna, Antonella Tripiciano, Cristina Mussini |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Medicine (General) HIV residual viremia Human immunodeficiency virus (HIV) HIV Infections CD8-Positive T-Lymphocytes HIV Antibodies medicine.disease_cause Lymphocyte Activation 0302 clinical medicine Anti-Tat antibodies Anti-Tat cellular immunity CD4+ T cells HIV immune activation HIV reservoirs HIV-1 Tat Perspective for clinical implications Antiretroviral Therapy Highly Active B-Lymphocytes Biomarkers CD4 Lymphocyte Count HIV-1 Host-Pathogen Interactions Humans Immunophenotyping Viral Load tat Gene Products Human Immunodeficiency Virus virus diseases General Medicine 030220 oncology & carcinogenesis Medicine tat Gene Products Human Immunodeficiency Virus Cart Antiretroviral Therapy Viremia General Biochemistry Genetics and Molecular Biology Virus 03 medical and health sciences R5-920 Immune system Immunity medicine Highly Active business.industry biochemical phenomena metabolism and nutrition medicine.disease 030104 developmental biology Immunology bacteria business Serostatus CD8 |
| Zdroj: | EBioMedicine, Vol 66, Iss, Pp 103306-(2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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