Background: Tenofovir with full-dose didanosine has been associated with paradoxical CD4+ T cell decrease despite virological suppression. We investigated whether tenofovir plus didanosine at a weight-adjusted dosage could be responsible for such an effect, and factors associated with CD4+ T cell count evolution under this combination. Methods: This was a prospective observational multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts). Patients with HIV plasma viral load suppression for ≥6 months who switched to an antiretroviral combination including tenofovir plus didanosine were studied, as long as virological success was maintained. CD4+ T cell count variations over time (slopes) were compared before and after switching to tenofovir plus didanosine using linear mixed models and segmented regression analysis. Results: Annual time-weighted CD4+ T cell count slope did not change significantly after the prescription of tenofovir plus didanosine: it was 14 cells/mm3 [95% confidence interval (CI) - 7 to 35] from month -24 to month -12, 12 cells/mm3 (95% CI -14 to 38) from month -12 to the time of switching, 30 cells/mm3 (95% CI 5-55) from switching to month 112 and 15 cells/mm3 (95% CI -8 to 39) from month +12 to month +24 after switching to tenofovir plus didanosine. No significant change in the slope of the segment after the switch to tenofovir plus didanosine-containing regimens when compared with the segment preceding the intervention was found (CD4+ T cell count slope change: 24 cells/mm3; 95% CI -10 to 58). Similar results were obtained using CD4+ T cell percentage over total lymphocytes. The significant independent predictors of lower CD4+ T cell count slope were older age (P = 0.006), lower nadir CD4+ T cell count (P < 0.001) and positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated creatinine clearance was an additional independent predictor of lower CD4+ T cell count slope (P = 0.02), but only after excluding nadir CD4+ T cell count. Conclusions: Tenofovir plus didanosine (weight-adjusted dosage) was not associated with paradoxical CD41 T cell decrease in our patients maintaining undetectable HIV plasma viral load for a maximum of 24 months after switching. Several factors could explain variability in CD4+ T cell count evolution in these patients. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Torti, C., Lapadula, G., Barreiro, P., Soriano, V., Mandalia, S., De Silvestri, A., et al. (2007). CD4+ T cell evolution and predictors of its trend before and after tenofovir/didanosine backbone in the presence of sustained undetectable HIV plasma viral load. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 59(6), 1141-1147 [10.1093/jac/dkm100].
CD4+ T cell evolution and predictors of its trend before and after tenofovir/didanosine backbone in the presence of sustained undetectable HIV plasma viral load
Lapadula G.Co-primo
;Suter F.;Migliorino G.;
2007
Abstract
Background: Tenofovir with full-dose didanosine has been associated with paradoxical CD4+ T cell decrease despite virological suppression. We investigated whether tenofovir plus didanosine at a weight-adjusted dosage could be responsible for such an effect, and factors associated with CD4+ T cell count evolution under this combination. Methods: This was a prospective observational multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts). Patients with HIV plasma viral load suppression for ≥6 months who switched to an antiretroviral combination including tenofovir plus didanosine were studied, as long as virological success was maintained. CD4+ T cell count variations over time (slopes) were compared before and after switching to tenofovir plus didanosine using linear mixed models and segmented regression analysis. Results: Annual time-weighted CD4+ T cell count slope did not change significantly after the prescription of tenofovir plus didanosine: it was 14 cells/mm3 [95% confidence interval (CI) - 7 to 35] from month -24 to month -12, 12 cells/mm3 (95% CI -14 to 38) from month -12 to the time of switching, 30 cells/mm3 (95% CI 5-55) from switching to month 112 and 15 cells/mm3 (95% CI -8 to 39) from month +12 to month +24 after switching to tenofovir plus didanosine. No significant change in the slope of the segment after the switch to tenofovir plus didanosine-containing regimens when compared with the segment preceding the intervention was found (CD4+ T cell count slope change: 24 cells/mm3; 95% CI -10 to 58). Similar results were obtained using CD4+ T cell percentage over total lymphocytes. The significant independent predictors of lower CD4+ T cell count slope were older age (P = 0.006), lower nadir CD4+ T cell count (P < 0.001) and positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated creatinine clearance was an additional independent predictor of lower CD4+ T cell count slope (P = 0.02), but only after excluding nadir CD4+ T cell count. Conclusions: Tenofovir plus didanosine (weight-adjusted dosage) was not associated with paradoxical CD41 T cell decrease in our patients maintaining undetectable HIV plasma viral load for a maximum of 24 months after switching. Several factors could explain variability in CD4+ T cell count evolution in these patients. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
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