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

Carlo Torti, Giuseppe Lapadula, Pablo Barreiro, Vicente Soriano, Sundhiya Mandalia, Annalisa De Silvestri, Fredy Suter, Franco Maggiolo, Andrea Antinori, Francesco Antonucci, Renato Maserati, Issa El Hamad, Piera Pierotti, Laura Sighinolfi, Guglielmo Migliorino, Nicoletta Ladisa, Giampiero Carosi

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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.

Original languageEnglish
Pages (from-to)1141-1147
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume59
Issue number6
DOIs
Publication statusPublished - Jun 2007

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Tenofovir
Didanosine
Viral Load
CD4 Lymphocyte Count
HIV
T-Lymphocytes
Confidence Intervals

Keywords

  • Antiretroviral therapy
  • CD4 cell count
  • Immune recovery
  • Immune toxicity

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

Cite this

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. / Torti, Carlo; Lapadula, Giuseppe; Barreiro, Pablo; Soriano, Vicente; Mandalia, Sundhiya; De Silvestri, Annalisa; Suter, Fredy; Maggiolo, Franco; Antinori, Andrea; Antonucci, Francesco; Maserati, Renato; El Hamad, Issa; Pierotti, Piera; Sighinolfi, Laura; Migliorino, Guglielmo; Ladisa, Nicoletta; Carosi, Giampiero.

In: Journal of Antimicrobial Chemotherapy, Vol. 59, No. 6, 06.2007, p. 1141-1147.

Research output: Contribution to journalArticle

Torti, C, Lapadula, G, Barreiro, P, Soriano, V, Mandalia, S, De Silvestri, A, Suter, F, Maggiolo, F, Antinori, A, Antonucci, F, Maserati, R, El Hamad, I, Pierotti, P, Sighinolfi, L, Migliorino, G, Ladisa, N & Carosi, G 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, vol. 59, no. 6, pp. 1141-1147. https://doi.org/10.1093/jac/dkm100
Torti, Carlo ; Lapadula, Giuseppe ; Barreiro, Pablo ; Soriano, Vicente ; Mandalia, Sundhiya ; De Silvestri, Annalisa ; Suter, Fredy ; Maggiolo, Franco ; Antinori, Andrea ; Antonucci, Francesco ; Maserati, Renato ; El Hamad, Issa ; Pierotti, Piera ; Sighinolfi, Laura ; Migliorino, Guglielmo ; Ladisa, Nicoletta ; Carosi, Giampiero. / 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. In: Journal of Antimicrobial Chemotherapy. 2007 ; Vol. 59, No. 6. pp. 1141-1147.
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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.",
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T1 - 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

AU - Torti, Carlo

AU - Lapadula, Giuseppe

AU - Barreiro, Pablo

AU - Soriano, Vicente

AU - Mandalia, Sundhiya

AU - De Silvestri, Annalisa

AU - Suter, Fredy

AU - Maggiolo, Franco

AU - Antinori, Andrea

AU - Antonucci, Francesco

AU - Maserati, Renato

AU - El Hamad, Issa

AU - Pierotti, Piera

AU - Sighinolfi, Laura

AU - Migliorino, Guglielmo

AU - Ladisa, Nicoletta

AU - Carosi, Giampiero

PY - 2007/6

Y1 - 2007/6

N2 - 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.

AB - 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.

KW - Antiretroviral therapy

KW - CD4 cell count

KW - Immune recovery

KW - Immune toxicity

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