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.
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.



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.



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).



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.
Clinic of Infectious Diseases, Department of Health Sciences, San Paolo Hopsital, University of Milan, Milan, Italy.
Camilla
C
Tincati
Alessia
A
Savoldi
E Stefania
ES
Cannizzo
Giusi M
GM
Bellistrì
Roberta
R
Termini
Marzia
M
Garau
Daniela
D
Mancusi
Antonella
A
d'Arminio Monforte
Giulia
G
Marchetti
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D000069454:Darunavir / Q000008:administration & dosage / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000627:therapeutic use; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D017967:Zinc Compounds; D009525:Niacin; C038070:efavit; D011736:Pyridoxine; D019438:Ritonavir; D001205:Ascorbic Acid; D000069454:Darunavir