Department of Infectious Diseases, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
AIDS Rev. 2018;20(4):179-186. doi: 10.24875/AIDSRev.M18000026.
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.
抗逆转录病毒疗法的进步使得 HIV 感染者的生存状况得到了显著改善。然而,HIV 的治愈仍然难以实现,需要终身治疗。为了减少长期药物暴露、毒性和成本,同时保持病毒抑制,人们尝试探索使用最新的、更有效的抗逆转录病毒药物,是否可以采用少于三联疗法的维持策略。虽然单药治疗由于耐药性选择而失败,但一些双联方案已被证明在病毒抑制的患者中序贯使用时是有效的,这些患者采用标准三联方案治疗。此外,复方制剂的出现使得长期药物依从性更容易实现。在此,我们回顾了多替拉韦(DTG)和利匹韦林(RPV)(Juluca)新的单片治疗方案的现有经验。这是首个批准的二药单片方案,也是首个双核苷类药物节省型复方制剂。两项随机、非劣效性临床试验(SWORD-1 和 -2)和五项观察性研究评估了 DTG-RPV 在治疗经验丰富的患者中的疗效。尽管纳入标准不同,但超过 95%的患者至少在 48 周内保持血浆 HIV-RNA 不可检测。与病毒学疗效非劣效于三联方案一致,DTG-RPV 的耐受性良好,由于不良事件而停药的比例仅为 0.8-7.9%。此外,与从蛋白酶抑制剂转换的患者相比,脂代谢谱得到改善,与从替诺福韦二吡呋酯转换的患者相比,肾和骨生物标志物也得到改善。最后,对 DTG-RPV 耐药的情况罕见。总之,DTG-RPV 是一种新型的双联复方制剂,如果病毒对两种药物均完全敏感,可有效且安全地用于病毒抑制的治疗经验丰富的患者。其独特的特性使其成为长期治疗方案或终身维持 HIV 治疗的最佳选择之一。