Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV.
Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV.
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DOI：
10.1128/aac.00584-22
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发表时间：
2022-12-20
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
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双氢青蒿素-哌喹是一种以青蒿素为基础的联合疗法，已被确定为妊娠期疟疾间歇预防性治疗的一种有希望的药物。然而，在感染艾滋病毒（PLWH）的孕妇中，以依非韦伦为基础的抗逆转录病毒治疗（ART）可显著减少哌喹的血浆暴露。在一项开放标签、非随机、固定序列、药代动力学研究中，我们比较了13名妊娠中期或晚期双氢青蒿素-哌喹与以依非韦伦为基础的抗逆转录病毒疗法和以曲地韦为基础的抗逆转录病毒疗法联合使用3天疗程中的哌喹血药浓度。在以依非韦伦为基础的抗逆转录病毒治疗期间和切换到以氟替克韦为基础的抗逆转录病毒治疗后的28天内测量哌喹浓度。进行非区隔分析，生成几何平均比（GMRs）和90%置信区间（CIs）来比较这两个治疗期哌喹的药代动力学参数。与以依非韦伦为基础的抗逆转录病毒治疗相比，双氢青蒿素-哌喹和多替格雷韦为基础的抗逆转录病毒治疗联合使用导致总体哌喹暴露增加57%（浓度-时间曲线下面积从0到672 h [AUC0-672 h]） （GMR, 1.57; 90% CI， 1.28至1.93）。哌喹第7天的浓度也高出63% (GMR, 1.63; 90% CI， 1.29至2.11)，而第28天的浓度几乎高出三倍（GMR, 2.96; 90% CI， 2.25至4.07）。然而，最大哌喹浓度（Cmax）保持相似（GMR, 1.09; 90% CI, 0.79 ~ 1.49）。双氢青蒿素-哌喹耐受性良好，在这项小型研究中未观察到与药物相关的严重不良事件。与以依非韦伦为基础的抗逆转录病毒治疗（一种已知的哌喹代谢诱导剂）相比，以多替格雷韦为基础的抗逆转录病毒治疗导致总体哌喹暴露增加，其药代动力学参数值与先前发表的孕妇和非孕妇的相似。我们的研究结果表明，双氢青蒿素-哌喹的疗效将保留在孕妇使用多替格拉韦。（本研究已在PACTR.samrc.ac.za [PACTR201910580840196]注册。）
Dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, has been identified as a promising agent for intermittent preventive treatment of malaria in pregnancy. However, in pregnant women living with HIV (PLWH), efavirenz-based antiretroviral therapy (ART) significantly reduces the plasma exposure of piperaquine. In an open-label, nonrandomized, fixed-sequence, pharmacokinetic study, we compared piperaquine plasma concentrations in 13 pregnant women during a 3-day treatment course of dihydroartemisinin-piperaquine when coadministered with efavirenz-based versus dolutegravir-based ART in the second or third trimester of pregnancy. Piperaquine concentrations were measured over a 28-day period, while on efavirenz-based ART and after switching to dolutegravir-based ART. Noncompartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare piperaquine pharmacokinetic parameters between these two treatment periods. Compared with efavirenz-based ART, coadministration of dihydroartemisinin-piperaquine and dolutegravir-based ART resulted in a 57% higher overall piperaquine exposure (area under the concentration-time curve from 0 to 672 h [AUC0–672 h]) (GMR, 1.57; 90% CI, 1.28 to 1.93). Piperaquine’s day 7 concentrations were also 63% higher (GMR, 1.63; 90% CI, 1.29 to 2.11), while day 28 concentrations were nearly three times higher (GMR, 2.96; 90% CI, 2.25 to 4.07). However, the maximum piperaquine concentration (Cmax) remained similar (GMR, 1.09; 90% CI, 0.79 to 1.49). Dihydroartemisinin-piperaquine was well tolerated, with no medication-related serious adverse events observed in this small study. Compared with efavirenz-based ART, a known inducer of piperaquine metabolism, dolutegravir-based ART resulted in increased overall piperaquine exposure with pharmacokinetic parameter values that were similar to those published previously for pregnant and nonpregnant women. Our findings suggest that the efficacy of dihydroartemisinin-piperaquine will be retained in pregnant women on dolutegravir. (The study was registered on PACTR.samrc.ac.za [PACTR201910580840196].)
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DOI：
10.1016/s1473-3099(16)30378-4
发表时间：
2017-02
期刊：
The Lancet. Infectious diseases
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作者：
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作者：
Lourens, Chris;Lindegardh, Niklas;Tarning, Joel
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Tarning, Joel
影响因子：
2.9
作者：
González R;Nhampossa T;Mombo-Ngoma G;Mischlinger J;Esen M;Tchouatieu AM;Pons-Duran C;Dimessa LB;Lell B;Lagler H;Garcia-Otero L;Zoleko Manego R;El Gaaloul M;Sanz S;Piqueras M;Sevene E;Ramharter M;Saute F;Menendez C
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Menendez C
DOI：
10.1136/ebmed-2016-110438
发表时间：
2016-08
期刊：
Evidence-based medicine
影响因子：
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作者：
Hill J;Kuile FO
通讯作者：
Kuile FO