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:


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.

[1]
Günthard HF, Saag MS, Benson CA, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2016 Recommendations of the International Antiviral Society-USA Panel. JAMA 2016; 316(2)191210
[http://dx.doi.org/10.1001/jama.2016.8900]
[2]
Roncier C. Rapport Morlat 2016: Des nouveautés dans la prise en charge des personnes vivant avec le VIH. 2016 [cité 11 juill 2018]. Disponible sur: http://vih.org/20161019/rapport-morlat-2016-nouveautes-prise-en-charge-personnes-vivant-vih/ [Accessed July 11, 2018]
[3]
Dossou-Yovo F, Mamadou G, Soudy ID, et al. Metronidazole or cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs. PLoS One 2015; 9(2)e89943
[http://dx.doi.org/10.1371/journal.pone.0089943]
[4]
Solas C, Muret P. Groupe suivi therapeutique pharmacolo-gique de la societe francaise de pharmacologie et de thera-peutique. Therapie 2011; 66(3): 213-9.
[http://dx.doi.org/10.2515/therapie/2011032] [PMID: 21819805]
[5]
Busti AJ, Hall RG, Margolis DM. Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy 2004; 24(12): 1732-47.
[http://dx.doi.org/10.1592/phco.24.17.1732.52347] [PMID: 15585441]
[6]
Wen X, Wang J-S, Backman JT, Laitila J, Neuvonen PJ. Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively. Drug Metab Dispos 2002; 30(6): 631-5.
[http://dx.doi.org/10.1124/dmd.30.6.631] [PMID: 12019187]
[7]
Laprise C, Baril J-G, Dufresne S, Trottier H. Atazanavir and other determinants of hyperbilirubinemia in a cohort of 1150 HIV-positive patients: Results from 9 years of follow-up. AIDS Patient Care STDS 2013; 27(7): 378-86.
[http://dx.doi.org/10.1089/apc.2013.0009] [PMID: 23829329]
[8]
Gervasoni C, Meraviglia P, Minisci D, et al. Metabolic and kidney disorders correlate with high atazanavir concentrations in HIV-infected patients: Is it time to revise atazanavir dosages? PLoS One 2015; 10(4)e0123670
[http://dx.doi.org/10.1371/journal.pone.0123670] [PMID: 25875091]
[9]
Bertz RJ, Persson A, Chung E, et al. Pharmacokinetics and pharmacodynamics of atazanavir-containing antiretroviral regimens, with or without ritonavir, in patients who are HIV-positive and treatment-naïve. Pharmacother J Hum Pharmacol Drug Ther 33(3): 284-94.https://onlinelibrary-wiley-com.gate2.inist.fr/doi/abs/10.1002/phar.1205
[10]
Zhang D, Chando TJ, Everett DW, Patten CJ, Dehal SS, Hum-phreys WG. In vitro Inhibition of UDP glucuronosyl transferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation. Drug Metab Dispos 2005; 33(11) 172939
[http://dx.doi.org/dmd.aspetjournals.org/content/33/11/1729]
[11]
Rodríguez-Nóvoa S, Martín-Carbonero L, Barreiro P, et al. Genetic factors influencing atazanavir plasma concentrations and the risk of severe hyperbilirubinemia. AIDS 2007; 21(1): 41-6.
[http://dx.doi.org/10.1097/QAD.0b013e328011d7c1] [PMID: 17148966]
[12]
Pugliese P, Cuzin L, Enel P, et al. NADIS 2000, development of an electronic medical record for patients infected by HIV, HBV and HCV. Presse Medicale Paris Fr 1983 22 févr 2003; 32(7): 299-303.https://www.ncbi.nlm.nih.gov/pubmed/12610445
[PMID: 12610445]
[13]
Dellamonica P, Katlama C, Lévy-Bachelot L, Daures J-P, Finkielsztejn L. Abacavir (Ziagen®) use between 2003 and 2008 in France according to the electronic medical record NADIS®. Médecine Mal Infect 2018; 43(11): 46774.
[http://dx.doi.org/www. sciencedirect.com/science/article/pii/S0399077X1300293X]
[14]
Jung BH, Rezk NL, Bridges AS, Corbett AH, Kashuba ADM. Simultaneous determination of 17 antiretroviral drugs in human plasma for quantitative analysis with liquid chromatography-tandem mass spectrometry. Biomed Chromatogr 2007; 21(10): 1095-104.
[http://dx.doi.org/10.1002/bmc.865] [PMID: 17582235]
[15]
Smith DE, Jeganathan S, Ray J. Atazanavir plasma concentrations vary significantly between patients and correlate with increased serum bilirubin concentrations. HIV Clin Trials 2006; 7(1): 34-8.
[http://dx.doi.org/10.1310/0KX0-H9VH-99EE-5D0L] [PMID: 16632461]
[16]
Cleijsen RMM, van de Ende ME, Kroon FP, et al. Therapeutic drug monitoring of the HIV protease inhibitor atazanavir in clinical practice. J Antimicrob Chemother 2007; 60(4): 897-900.
[http://dx.doi.org/10.1093/jac/dkm298] [PMID: 17704117]
[17]
Moltó J, Deig E, Valle M, et al. Effect of nevirapine on the steady-state trough concentrations of atazanavir in HIV-infected patients receiving atazanavir/ritonavir. Ther Drug Monit 2010; 32(1): 93-6.
[http://dx.doi.org/10.1097/FTD.0b013e3181cb479f] [PMID: 20040897]
[18]
VigiBase [Internet]. [cité 2 août 2018]. Disponible sur: https://www.who-umc.org/vigibase/vigibase/ [Accessed August 2 2018].
[19]
Hautekeete ML. Hepatotoxicity of antibiotics. Acta Gastroenterol Belg 1995; 58(3-4): 290-6.
[PMID: 7491842]
[20]
Lee BL, Delahunty T, Safrin S. The hydroxylamine of sulfamethoxazole and adverse reactions in patients with acquired immunodeficiency syndrome. Clin Pharmacol Ther 1994; 56(2): 184-9.
[http://dx.doi.org/10.1038/clpt.1994.122] [PMID: 8062495]
[21]
Kobuchi S, Fukushima K, Aoyama H, Ito Y, Sugioka N, Takada K. Effects of oxidative stress on the pharmacokinetics and hepatic metabolism of atazanavir in rats. Free Radic Res 2013; 47(4): 291-300.
[http://dx.doi.org/10.3109/10715762.2013.770149] [PMID: 23351068]
[22]
Sturgill MG, Seibold JR, Boruchoff SE, Yeh KC, Haddix H, Deutsch P. Trimethoprim/sulfamethoxazole does not affect the steady-state disposition of indinavir. J Clin Pharmacol 1999; 39(10): 1077-84.
[http://dx.doi.org/10.1177/00912709922011737] [PMID: 10516943]
[23]
Cañas E, Pachon J, Garcia-Pesquera F, et al. Absence of effect of trimethoprim-sulfamethoxazole on pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus. Antimicrob Agents Chemother 2018; 40(1): 2303. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC163089/
[24]
Cattaneo D, Meraviglia P, Cozzi V, Baldelli S, Milani G, Clementi E. Atypical pharmacokinetics of atazanavir in an HIV-1-infected patient. Fundam Clin Pharmacol 2018; 26(2): 2046.
[http://dx.doi.org/10.1111/j.1472-8206.2010.00905]
[25]
Cattaneo D, Ripamonti D, Baldelli S, Cozzi V, Fucile S, Clementi E. Limited sampling strategies for the estimation of atazanavir daily exposure in HIV-infected patients. Fundam Clin Pharmacol 2018; 27(2): 216-22.


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Article Details

VOLUME: 14
ISSUE: 3
Year: 2019
Published on: 05 April, 2019
Page: [214 - 223]
Pages: 10
DOI: 10.2174/1574884714666190405160612

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