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Recovery of CD4+ T cells after switch to a nucleoside free regimen in patients with poor immunologic response despite complete HIV-RNA suppression
Presented by Gerd Fätkenheuer, Germany.
Lehmann C.1, Hofmann A.1, Cornely O.1, Jung N.1, Hartmann P.1, Schmeisser N.1, Wyen C.1, Fätkenheuer G.1
1University Hospital, Infectious Diseases, Köln, Germany
Objectives: ART usually leads to suppression of HIV load and rapid rise of CD4+ T- cells. In some patients poor recovery of CD4+ T- cells despite optimal viral suppression on ART is observed. As some combinations of nucleoside analogues (NA) have been associated with paradoxical depletion of CD4+ T- cells, we postulated that the change from a NA containing to a NA free regimen could improve immunological parameters.
Methods: 15 HIV-1 infected patients on NA containing ART with undetectable HIV and CD4+ T cells < 250/mL for at least 6 months were included in this study after informed consent. Treatment was switched to atazanavir (ATV) (300mg qd), saquinavir (SQV, 1000mg bid) and ritonavir (RTV, 100mg qd). The clinical course was assessed monthly for 48 weeks. T cell activation (CD38+HLA-DR+) on CD4+ and CD8+ T- cells were longitudinally (0, 24 and 48 weeks) determined and compared to good immunologic (IgR) responders with ART (n=10) and patients with high CD4+ T cells without ART (n=9) by flow cytometry using PBMC.
Results: Median [IQR], age [yrs.]: 46 [38-62]; male: n=11, 66% CDC stage C3, CD4+ T cells/µL: 197 [130-220], 10% [7-17]; months on ART: 20, [6-114]. The regimen was well tolerated, 1 patient discontinued. HIV RNA remained < 50 copies in 14 patients, CD4+ T cells improved significantly (week 24: 230µL (14%), [170-290, 10-17%], week 48: 260/ml, 17% [195-415, 13.5-18.5%]). Activation markers did longitudinally not change and in comparison to IgR. Subjects with detecable HIV-RNA and high CD4+ T- cells demonstrated higher expression of CD38 on CD4+ and CD8+ T cells and HLA-DR on CD8+ T cells (p<0.05).
Conclusions: The boosted double PI combination of ATV/SQV may be an effective and well-tolerated NA-sparing treatment strategy for patients with poor immunologic response despite undetecable viraemia. Activation markers of T- cells were not significantly altered after 48 weeks and seem not to be responsible for the poor immunologic response.
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