Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
J Antimicrob Chemother. 2022 May 29;77(6):1733-1737. doi: 10.1093/jac/dkac081.
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.
在撒哈拉以南非洲，疟疾和 HIV 感染的负担重叠。在疟疾中度至高度传播强度的环境中，HIV 阳性孕妇（PLWH）既需要接受抗逆转录病毒治疗（ART），也需要接受间歇性预防治疗（IPT）。二氢青蒿素/哌喹已被确定为磺胺多辛/乙胺嘧啶替代物，适用于 IPT。然而，另一种抗疟药物青蒿琥酯/阿莫地喹，与二氢青蒿素/哌喹相似，先前已被证明会降低非孕妇成人中多替拉韦的暴露量。
研究二氢青蒿素/哌喹对接受基于多替拉韦的 ART 的孕妇中多替拉韦血浆暴露的影响。
我们在马拉维开展了一项开放性、非随机、固定序列、药代动力学研究，纳入了 12 名处于妊娠第二或第三孕期的 HIV 阳性孕妇。在接受推荐的 3 天二氢青蒿素/哌喹治疗剂量后，我们在 24 小时内测量了多替拉韦的浓度，在这两个治疗期之前和之后分别进行了测量。我们进行了非房室分析，并生成了几何均数比值（GMR）和 90%置信区间（CI），以比较两种治疗期之间多替拉韦的药代动力学参数。
二氢青蒿素/哌喹与多替拉韦联合使用，使多替拉韦的总体暴露量（AUC0-24）和 Cmax 分别增加了 30%（GMR 1.30；90%CI 1.11-1.52）和 31%（GMR 1.31；90%CI 1.13-1.51）。多替拉韦谷浓度（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。
二氢青蒿素/哌喹可与基于多替拉韦的 ART 联合用于孕妇，因为多替拉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，确保了其疗效，而在这项小型研究中未观察到任何临床意义上的不良事件。
