Abstract
BackgroundNRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients.MethodsBiomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts.ResultsAfter 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs.ConclusionsThe implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.
Highlights
nucleoside(tide) reverse transcriptase inhibitors (NRTIs)-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters
There were no differences in baseline characteristics between this subgroup and the patients who remained in a combination of 2 NRTIs and a PI
Higher CD127 T‐cell levels in patients on a NRTI‐sparing‐combination antiretroviral therapy (cART) After 48 weeks of suppressive cART, effector memory (TEM) CD4+ CD127+ T-cell levels were higher in the NRTI-sparing-cART group compared to the NRTIcART group (p = 0.017 in the unadjusted analysis and p = 0.043 after adjusting for basal CD4, CD8 and nadir CD4 T-cell counts to offset the difference found at baseline) (Fig. 1a)
Summary
NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. Defects as immune senescence and disturbed T-cell differentiation occur even after long-term suppressive cART [3]. These alterations may underlie the mechanisms causing non-AIDS events, a current major mortality cause in otherwise successfully treated HIV-infected patients [4]. NRTI-sparing regimens seem to exert favourable profiles on T-cell homeostasis-associated parameters in pre-treated and naïve HIV-infected patients [9, 10]
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