Effect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV.
Effect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV.
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DOI：
10.1093/jac/dkac081
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发表时间：
2022-05-29
影响因子：
5.2
通讯作者：
Barnes, Karen, I
中科院分区：
文献类型：
--
作者：
Banda, Clifford G.;Nkosi, Dumisile;Allen, Elizabeth;Workman, Lesley;Madanitsa, Mwayiwawo;Chirwa, Marumbo;Kapulula, Mayamiko;Muyaya, Sharon;Munharo, Steven;Wiesner, Lubbe;Phiri, Kamija S.;Mwapasa, Victor;Ter Kuile, Feiko O.;Maartens, Gary;Barnes, Karen, I
在撒哈拉以南非洲，疟疾和艾滋病毒感染的负担重叠。在中度至高度疟疾传播强度的环境中，感染艾滋病毒（PLWH）的孕妇需要接受ART和疟疾间歇性预防治疗（IPTp）。双氢青蒿素/哌喹已被确定为一种有前途的替代磺胺嘧啶/乙胺嘧啶的IPTP。然而，另一种抗疟药物青蒿琥酯/阿莫地喹，类似于双氢青蒿素/哌喹，以前被证明可以减少非妊娠成人的度鲁特韦暴露。为了研究双氢青蒿素/哌喹对接受以度鲁特韦为基础的ART的孕妇的度鲁特韦血浆暴露的影响。我们在马拉维的PLWH中进行了一项开放标签、非随机、固定序列的药代动力学研究。在推荐的3天治疗剂量的双氢青蒿素/哌喹之前和之后的24小时内，在12名妊娠中期或晚期的孕妇中测量多鲁特韦浓度。 进行非房室分析，并生成几何均值比（GMR）和90% CI，以比较两个治疗期之间的度鲁特韦药代动力学参数。双氢青蒿素/哌喹和度鲁特韦联合给药使度鲁特韦的总体暴露量（AUC 0 -24）和Cmax分别增加30%（GMR 1.30; 90% CI 1.11-1.52）和31%（GMR 1.31; 90% CI 1.13-1.51）。度鲁特韦谷浓度（C24）增加了42%（GMR 1.42; 90% CI 1.09-1.85）。联合治疗耐受性良好，未观察到严重不良事件。双氢青蒿素/哌喹可与基于度鲁特韦的ART一起用于孕妇，因为度鲁特韦暴露量的适度增加（与先前发表的药代动力学参数值相似）可确保其疗效，且在这项小型研究中未观察到任何临床显著不良事件。
In sub-Saharan Africa, the burdens of malaria and HIV infections overlap. In settings with moderate-to-high malaria transmission intensity, pregnant women living with HIV (PLWH) require both ART and malaria intermittent preventive treatment (IPTp). Dihydroartemisinin/piperaquine has been identified as a promising alternative to sulfadoxine/pyrimethamine for IPTp. However, another antimalarial drug, artesunate/amodiaquine, similar to dihydroartemisinin/piperaquine, was previously shown to reduce dolutegravir exposure in non-pregnant adults. To investigate the effect of dihydroartemisinin/piperaquine on dolutegravir plasma exposure in pregnant women on dolutegravir-based ART. We conducted an open-label, non-randomized, fixed-sequence, pharmacokinetic study in PLWH in Malawi. Dolutegravir concentrations were measured over a 24 h period, before and after the recommended 3 day treatment dose of dihydroartemisinin/piperaquine in 12 pregnant women in their second or third trimester. Non-compartmental analysis was performed, and geometric mean ratios (GMRs) and 90% CIs were generated to compare dolutegravir pharmacokinetic parameters between the two treatment periods. Co-administration of dihydroartemisinin/piperaquine and dolutegravir increased dolutegravir’s overall exposure (AUC0–24) and Cmax by 30% (GMR 1.30; 90% CI 1.11–1.52) and 31% (GMR 1.31; 90% CI 1.13–1.51), respectively. The dolutegravir trough (C24) concentration increased by 42% (GMR 1.42; 90% CI 1.09–1.85). The combined treatments were well tolerated with no serious adverse events observed. Dihydroartemisinin/piperaquine may be administered with dolutegravir-based ART in pregnant women as the modest increase in dolutegravir exposure, similar to pharmacokinetic parameter values published previously, ensures its efficacy without any clinically significant adverse events observed in this small study.
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