T-Cell Phenotype and Function following a First cART Regimen Containing Either a Protease Inhibitor or a Non-Nucleoside Reverse Transcriptase Inhibitor in HIV-Infected Late Presenters: Results from a Retrospective,ex vivo Study

Abstract

Background

We aimed to comparatively assess darunavir/ ritonavir (DRV/r) and efavirenz (EFV)-based first-line cART regimens in the reconstitution of T-cell phenotype and function in HIV-infected, late presenter subjects.

Methods

Retrospective, ex vivo study on stored peripheral blood mononuclear cell samples of cART-naive, HIV-infected individuals with CD4⁺ T-cell counts <50>250/μl upon cART initiation with either DRV/r or EFV as third drugs of standard antiretroviral regimens. CD4⁺ and CD8⁺ T-cell maturation (CCR7/CD45RA) and proliferation (Ki67), CD8⁺ T-cell activation (CD38/HLA-DR) as well as HIV- and cytomegalovirus (CMV)-specific responses (CD4/CD8/IL-2/IFN-γ) were studied by flow cytometry at baseline (T0), T3, T6 and T12 months. Soluble inflammatory markers (IL-6 and sCD14) were measured in plasma at T0 and T12. Wilcoxon and Mann–Whitney tests were used for statistics.

Results

A total of 19 patients started DRV/r and 15 EFV. Both regimens accounted for suppression of the HIV RNA load (<40 copies/ml), reconstitution of absolute CD4⁺ T-cells and CD4⁺/CD8⁺ T-cell ratio. All study participants displayed a significant decrease of activated HLA-DR⁺CD38⁺ CD8⁺ T-cells at all study time points, yet no differences were found between study groups in T-cell activation and maturation phenotype. From a functional standpoint, only individuals receiving DRV/r displayed transitory recovery of HIV-specific IL-2⁺IFN-γ^- CD4⁺ T-cells (T3: P=0.006) and IL-2^-IFN-γ⁺ CD8⁺ T-cells (T3: P=0.032).

Conclusions

DRV/r- and EFV-based regimens have an equal effect on T-cell phenotype and function in HIV late presenters. A temporary restoration of HIV-specific T-cell immunity early in the course of therapy with DRV/r possibly implies a more effective control over HIV in the first months following a PI/r-based regimen, even at late stage of disease.

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