Joe Miantezila B, Roland Landman, Laurent Chouchana, Patrick Lê M, Sawoo Olivier, Gaston Tona L, Bruno Eto, Gilles Peytavin, Philippe Pochart
EA4065 Ecosystème Intestinal, Probiotique, Antibiotiques, Université Paris Descartes SPC, Paris, France.
Unité de Pharmacologie Clinique, Université de Kinshasa, Kinshasa, RD, Congo.
Curr Clin Pharmacol. 2019;14(3):214-223. doi: 10.2174/1574884714666190405160612.
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.
We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches.
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.
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).
This study showed a relevant concomitant use between Cotrimoxazole and ATV based on TDM and PV approaches.
复方新诺明是晚期HIV感染患者机会性感染一级预防中使用的主要抗生素。该药物可抑制阿扎那韦（ATV）的一种代谢途径，如细胞色素P450（CYP）2C8/2C9，可能会干扰其安全性和疗效。
我们通过治疗药物监测（TDM）和药物警戒（PV）方法研究复方新诺明与ATV之间的药物相互作用（DDI）。
我们将一组接受复方新诺明治疗并采用基于ATV方案的患者与对照组进行比较。这项历史性队列分析使用了来自Dat'AIDS的HIV感染患者的数据，这些患者在门诊随访期间至少有两次ATV的最低血浆浓度（谷浓度）。同样，我们使用了来自VigiBase的国际药物警戒数据来评估ATV报告的高胆红素血症通知。
在TDM分析中，两组患者（接受复方新诺明治疗的患者和对照组）在主要基线特征方面几乎同质。在基于ATV的方案治疗至少六个月后，与对照组相比，ATV谷浓度的安全阈值没有显著差异[调整后的优势比（aOR）为1.4（95%置信区间：0.5 - 4.4）]。我们在ATV谷浓度的疗效阈值方面也观察到了类似的结果。关于PV分析，当复方新诺明同时使用时，ATV发生高胆红素血症没有差异，调整后的报告优势比（aROR）为0.9（95%置信区间：0.6至1.2）。
本研究基于TDM和PV方法显示复方新诺明与ATV可以联合使用。
