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

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 lowlevel 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 lowlevel 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. (C) 2021 The Author(s). Published by Elsevier B.V.

Automated summary

The study found that anti-Tat immunity is significantly associated with higher CD4(+) T cell numbers, control of low-level viremia, and long-lasting CD4(+) T cell recovery, but not with decreased immune activation. CD4(+) T cell restoration is influenced by interactions among Tat immunity, residual viremia, and other immune determinants.