Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials.
Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials.
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DOI：
10.3389/fphar.2021.664875
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发表时间：
2021
影响因子：
5.6
通讯作者：
Hamers RL
中科院分区：
文献类型：
--
作者：
Lazarus G;Wangsaputra VK;Christianto;Louisa M;Soetikno V;Hamers RL
目的：研究长效注射暴露前预防（LAI PrEP），特别是卡波特韦（CAB-LA）和利匹韦林（RPV-LA）预防人类免疫缺陷病毒-1 （HIV-1）感染的安全性和药代动力学特征。方法：纳入在hiv未感染和/或健康患者中使用LAI PrEP的符合条件的随机试验，并使用修订后的Cochrane随机试验风险偏倚工具进行评估。在可行的情况下，使用随机效应模型对安全性结果进行荟萃分析，风险比及其95%置信区间作为常见效果度量。该协议注册号为PROSPERO CRD42020154772。结果：本系统综述纳入了8项研究，共666名受试者，其中5项（362名干预组志愿者）和4项（194名干预组志愿者）分别研究了CAB-LA和RPV-LA。我们发现CAB-LA和RPV-LA均具有良好的耐受性，因为它们在任何不良事件（AE）、严重AE和AE相关戒断方面的安全性与安慰剂相似。此外，药代动力学分析显示CAB-LA和RPV-LA具有良好的病毒抑制活性。在男性受试者中，肌内注射CAB-LA 600 mg Q8W优于CAB-LA 800 mg Q12W，而RPV-LA 1200 mg Q8W优于其他给药方案。虽然这些结果很有希望，但由于目前的证据有限，需要进一步的研究来证实RPV-LA的发现。结论：CAB-LA和RPV-LA具有良好的安全性和药动学特征。这些药物的预防效果正在三期试验中进行评估。
Objectives: To investigate the safety and pharmacokinetic profiles of long-acting injectable pre-exposure prophylaxis (LAI PrEP), notably cabotegravir (CAB-LA) and rilpivirine (RPV-LA), for the prevention of human immunodeficiency virus-1 (HIV-1) infection. Methods: Eligible randomized trials of LAI PrEP in HIV-uninfected and/or healthy patients were included and assessed with the Revised Cochrane risk-of-bias tool for randomized trials. Where feasible, a meta-analysis was performed for safety outcomes by using a random-effects model with risk ratios and their 95% confidence intervals as the common effect measure. The protocol was registered with PROSPERO CRD42020154772. Results: Eight studies cumulating a total of 666 participants were included in this systematic review, including five (362 intervention-arm volunteers) and four trials (194 intervention-arm volunteers) that investigated CAB-LA and RPV-LA, respectively. We found that both CAB-LA and RPV-LA were generally well-tolerated as their safety profiles were similar to placebo in terms of any adverse event (AE), serious AE, and AE-related withdrawals. Furthermore, pharmacokinetic analyses revealed favorable prospects in viral inhibitory activity of CAB-LA and RPV-LA. Intramuscular (IM) injection of CAB-LA 600 mg Q8W was superior to CAB-LA 800 mg Q12W in male participants, while the same was true for RPV-LA 1200 mg IM Q8W over other dosing regimens. Although these results are promising, further research is required to confirm the findings on RPV-LA as current evidence is limited. Conclusion: CAB-LA and RPV-LA have promising safety and pharmacokinetic profiles. The preventive efficacy of these agents is being evaluated in Phase 3 trials.
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通讯作者：
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