Concomitant Use of Cotrimoxazole and Atazanavir in HIV-infected Patients: A Therapeutic Drug Monitoring and Pharmacovigilance Based Dual Approach

Author(s): Miantezila B. Joe*, Landman Roland, Chouchana Laurent, Lê M. Patrick, Olivier Sawoo, Tona L. Gaston, Eto Bruno, Peytavin Gilles, Pochart Philippe

Journal Name: Current Clinical Pharmacology
Continued as Current Reviews in Clinical and Experimental Pharmacology

Volume 14 , Issue 3 , 2019

Graphical Abstract:


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.

Keywords: Cotrimoxazole, atazanavir, C-trough, adverse drug reactions, antiretroviral drugs, hyperbilirubinemia, prophylaxis.

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Article Details

Year: 2019
Published on: 05 April, 2019
Page: [214 - 223]
Pages: 10
DOI: 10.2174/1574884714666190405160612

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