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 language | English |
|---|---|
| Pages (from-to) | 1141-1147 |
| Number of pages | 7 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 59 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2007 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=34447572755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447572755&partnerID=8YFLogxK
U2 - 10.1093/jac/dkm100
DO - 10.1093/jac/dkm100
M3 - Article
C2 - 17434879
AN - SCOPUS:34447572755
VL - 59
SP - 1141
EP - 1147
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 6
ER -