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.

T-cell phenotype and function following a first cART regimen containing either a protease inhibitor or a non-nucleoside retrotranscriptase inhibitor in HIV-infected late presenters: results from a retrospective, ex vivo study / C. Tincati, A. Savoldi, E.S. Cannizzo, G.M. Bellistrì, R. Termini, M. Garau, D. Mancusi, A.D. Monforte, G. Marchetti. - In: ANTIVIRAL THERAPY. - ISSN 1359-6535. - 21:2(2016), pp. 133-142. ((Intervento presentato al 6. convegno Italian Conference on AIDS and Retroviruses tenutosi a Roma nel 2014 [10.3851/IMP2990].

T-cell phenotype and function following a first cART regimen containing either a protease inhibitor or a non-nucleoside retrotranscriptase inhibitor in HIV-infected late presenters: results from a retrospective, ex vivo study

C. Tincati
Primo
;
A. Savoldi
Secondo
;
E.S. Cannizzo;G.M. Bellistrì;G. Marchetti
Ultimo
2016

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.
Settore MED/17 - Malattie Infettive
10-set-2015
Article (author)
File in questo prodotto:
File Dimensione Formato  
AVT-15-OA-3504_Tincati_Web.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 312.46 kB
Formato Adobe PDF
312.46 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/350532
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact