Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir.

Détails

ID Serval
serval:BIB_5012641E36D5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir.
Périodique
Aids
Auteur⸱e⸱s
Karrer U., Ledergerber B., Furrer H., Elzi L., Battegay M., Cavassini M., Gayet-Ageron A., Hirschel B., Schmid P., Russotti M., Weber R., Speck R.F.
Collaborateur⸱rice⸱s
Swiss HIV Cohort Study
ISSN
0269-9370[print], 0269-9370[linking]
Statut éditorial
Publié
Date de publication
2005
Volume
19
Numéro
17
Pages
1987-1994
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
BACKGROUND: Antiretroviral therapy (ART) containing tenofovir disoproxil fumarate (TDF) and didanosine (ddI) has been associated with poor immune recovery despite virologic success. This effect might be related to ddI toxicity since ddI exposure is substantially increased by TDF. OBJECTIVE: To analyze whether immune recovery during ART with TDF and ddI is ddI-dose dependent.
DESIGN AND METHODS: A retrospective longitudinal analysis of immune recovery measured by the CD4 T-cell slope in 614 patients treated with ART containing TDF with or without ddI. Patients were stratified according to the tertiles of their weight-adjusted ddI dose: low dose (< 3.3 mg/kg), intermediate dose (3.3-4.1 mg/kg) and high dose (> 4.1 mg/kg). Cofactors modifying the degree of immune recovery after starting TDF-containing ART were identified by univariable and multivariable linear regression analyses.
RESULTS: CD4 T-cell slopes were comparable between patients treated with TDF and a weight-adjusted ddI-dose of < 4.1 mg/kg per day (n = 143) versus TDF-without-ddI (n = 393). In the multivariable model the slopes differed by -13 CD4 T cells/mul per year [95% confidence interval (CI), -42 to 17; P = 0.40]. In contrast, patients treated with TDF and a higher ddI dose (> 4.1 mg/kg per day, n = 78) experienced a significantly impaired immune recovery (-47 CD4 T cells/microl per year; 95% CI, -82 to -12; P = 0.009). The virologic response was comparable between the different treatment groups.
CONCLUSIONS: Immune recovery is impaired, when high doses of ddI (> 4.1 mg/kg) are given in combination with TDF. If the dose of ddI is adjusted to less than 4.1 mg/kg per day, immune recovery is similar to other TDF-containing ART regimen.
Mots-clé
Adenine/administration & dosage, Adenine/analogs & derivatives, Adult, CD4 Lymphocyte Count, Didanosine/administration & dosage, Didanosine/immunology, Dose-Response Relationship, Immunologic, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV Infections/drug therapy, HIV Infections/immunology, Humans, Male, Middle Aged, Phosphonic Acids/administration & dosage, Phosphonic Acids/immunology, RNA, Viral/analysis, Retrospective Studies, Reverse Transcriptase Inhibitors/administration & dosage, Reverse Transcriptase Inhibitors/immunology, Treatment Outcome
Pubmed
Web of science
Création de la notice
24/01/2008 20:44
Dernière modification de la notice
20/08/2019 14:06
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