New Dual Combination of Dolutegravir-Rilpivirine for Switching to Maintenance Antiretroviral Therapy.
New Dual Combination of Dolutegravir-Rilpivirine for Switching to Maintenance Antiretroviral Therapy.
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用于转为维持性抗逆转录病毒治疗的新型多替拉韦-利匹韦林双重组合。
作者：
E. Ribera
抗逆转录病毒疗法的进展大大改善了艾滋病毒感染者的存活率。然而，艾滋病毒的治愈仍然难以捉摸，需要终身治疗。试图减少长期药物暴露，毒性和成本，同时保持病毒抑制，导致探索是否可以使用最新的更有效的抗逆转录病毒药物的维持策略，少于三联疗法是可行的。虽然单药治疗未能选择耐药性，但一些双重组合已证明其在标准三联方案下顺序用于病毒抑制患者时的疗效。此外，共制剂的出现使长期药物依从性更容易。在此，我们回顾了目前的经验与新的单一片剂方案的度鲁特韦（DTG）和利匹韦林（RPV）（Juluca®）。这是第一个批准的双药单片剂方案和第一个双nuc-sparing联合制剂。两项随机、非劣效性临床试验（SWORD-1和SWORD-2）和五项观察性研究在有治疗经验的患者中评价了DTG-RPV。尽管有不同的入选标准，但超过95%的患者至少在48周内保持血浆HIV-RNA检测不到。沿着病毒学疗效不劣于三联方案，DTG-RPV的耐受性良好，因不良事件而停药的比例仅为0.8- 7.9%。此外，从蛋白酶抑制剂转换的患者的血脂谱以及从富马酸替诺福韦酯转换的患者的肾脏和骨生物标志物均有所改善。最后，DTG-RPV很少出现阻力失效。总之，DTG-RPV是一种新型的两药复方制剂，如果病毒对两种药物都完全敏感，则可以有效安全地用于病毒抑制的治疗经验患者。其独特的功能使这种药物作为长期方案或终身维持艾滋病毒治疗的最佳选择之一。
Advances in antiretroviral therapy have led to dramatic improvements in survival of HIV-infected persons. However, HIV cure remains elusive and lifelong treatment is needed. Attempts for reducing long-term drug exposure, toxicities, and cost, while maintaining viral suppression, have led to explore whether maintenance strategies with less than triple therapy could be feasible using the newest more potent antiretrovirals. While monotherapies have failed to do so with selection of drug resistance, some dual combinations have proven its efficacy when used sequentially in patients with viral suppression under standard triple regimens. Furthermore, the advent of coformulations makes easier long-term drug adherence. Herein, we review the current experience with the new single tablet regimen of dolutegravir (DTG) and rilpivirine (RPV) (Juluca®). It is the first approved two-drug single-tablet regimen and the first dual nuc-sparing coformulation. Two randomized, non-inferiority clinical trials (SWORD-1 and -2) and five observational studies have evaluated DTG-RPV in treatment-experienced patients. Despite distinct inclusion criteria, more than 95% of patients kept plasma HIV-RNA undetectable for at least 48 weeks. Along with virological efficacy being non-inferior to triple regimens, the tolerance of DTG-RPV was good, being discontinuations due to adverse events only 0.8-7.9%. Moreover, improvements were seen in lipid profiles in patients switched from protease inhibitors, and in renal and bone biomarkers in those switched from tenofovir disoproxil fumarate. Finally, resistance is rare failing on DTG-RPV. In summary, DTG-RPV is a novel two-drug coformulation that can be effectively and safely used in treatment-experienced patients with viral suppression if the virus is fully susceptible to both drugs. Its unique features make this drug one of the best options as long-term regimen or lifelong maintenance HIV therapy.