| アブストラクト | BACKGROUND: Cotrimoxazole is the main antibiotic used in primary prophylaxis for opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere with its safety and efficacy. OBJECTIVE: We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches. METHODS: We compared a group of patients treated with cotrimoxazole and receiving an ATV-based regimen to controls. This historical cohort analysis used data from Dat'AIDS in HIV-infected patients who had at least two lowest plasma concentrations (C-trough) of ATV during their outpatient follow-up. Likewise, we used the international pharmacovigilance data from VigiBase to evaluate the notifications of hyperbilirubinemia reported with ATV. RESULTS: In the TDM analysis, the two groups of patients (treated with cotrimoxazole and controls) were almost homogeneous concerning the main baseline features. After at least six months of ATVbased regimen, there was no significant difference in the safety threshold of the ATV C-trough [with an adjusted odds ratio (aOR) of 1.4 (95% CI: 0.5 - 4.4)] compared to controls. We observed similar results with the efficacy thresholds of ATV C-trough. Regarding the PV analysis, there was no difference in hyperbilirubinemia occurring with ATV when cotrimoxazole was concomitant, with an adjusted reporting odds ratio (aROR) of 0.9 (95% CI: 0.6 to 1.2). CONCLUSION: This study showed a relevant concomitant use between Cotrimoxazole and ATV based on TDM and PV approaches. |
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| 投稿者 | Joe, Miantezila B; Roland, Landman; Laurent, Chouchana; Patrick, Le M; Sawoo, Olivier; Gaston, Tona L; Bruno, Eto; Gilles, Peytavin; Philippe, Pochart |
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| 組織名 | EA4065 Ecosysteme Intestinal, Probiotique, Antibiotiques, Universite Paris;Descartes SPC, Paris, France.;Unite de Pharmacologie Clinique, Universite de Kinshasa, Kinshasa, RD, Congo.;Centre Regional de Pharmacovigilance, Hopital Cochin, Assistance publique-;Hopitaux de Paris, Paris, France.;Service des Maladies Infectieuses et Tropicales, Hopital Bichat, Paris, France.;IAME, UMR 1137, Universite Paris Diderot, Sorbonne Paris Cite and INSERM, Paris,;France.;EA7323 Evaluation therapeutique et pharmacologie perinatale et pediatrique,;Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.;AP-HP, Hopital Bichat-Claude Bernard, Laboratoire de Pharmaco-Toxicologie, Paris,;Microbial Ecology Laboratory (MIEL), CNAM, Paris, France.;TBC TransCell-Lab, Faculte de Medecine Xavier Bichat, Paris, France. |
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