Baril Jean-Guy, Angel Jonathan B, Gill M John, Gathe Joseph, Cahn Pedro, van Wyk Jean, Walmsley Sharon
Clinique médicale du Quartier latin, Montreal, Quebec, Canada.
Division of Infectious Diseases, University of Ottawa and the Ottawa Hospital, Ottawa, Ontario, Canada.
PLoS One. 2016 Feb 5;11(2):e0148231. doi: 10.1371/journal.pone.0148231. eCollection 2016.
We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection.
A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations.
Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels.
The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy.
我们回顾了当前有关抗逆转录病毒（ARV）保留疗法策略的文献，以确定这些新方案是否可被视为初治未接受过ARV治疗患者初始治疗的标准方案的合适替代方案，或作为病毒学抑制的HIV感染患者的转换疗法。
使用Biosis、德温特药物文件库、Embase、国际药学文摘、Medline、Pascal、SciSearch和TOXNET数据库，检索2000年1月至2014年4月发表的与HIV双重疗法相关的研究；七个主要试验注册库以及主要会议的摘要。使用预先确定的纳入标准，一个专家评审委员会对所有已识别试验的疗效、安全性结果及潜在局限性进行了严格评审和定性评估。
对16项针对初治未接受过ARV治疗人群的双重疗法方案研究进行了评判。蛋白酶抑制剂/利托那韦与整合酶抑制剂拉替拉韦或核苷类逆转录酶抑制剂拉米夫定联合应用的研究提供了支持双重疗法作用的最确凿证据。特别是，洛匹那韦/利托那韦或达芦那韦/利托那韦与拉替拉韦联合应用，以及洛匹那韦/利托那韦与拉米夫定联合应用，在治疗48周后显示出与标准三联疗法相当的疗效。对13项有ARV治疗经验、病毒学抑制患者的试验进行了评判。病毒学疗效结果不一。虽然关于毒性的总体数据有限，但与标准三联疗法相比，某些双重疗法方案在肾功能、骨矿物质密度和肢体脂肪变化方面可能具有优势；然而，一些双重组合可能会提高血脂或胆红素水平。
双重疗法方案的潜在益处包括毒性降低、耐受性和依从性提高以及成本降低。虽然此处回顾的数据为双重疗法方案的有效性和耐受性提供了有价值的见解，但这些潜在益处能否长期维持仍不清楚。需要进行有足够样本量且随访期更长的研究，以更明确地评估双重疗法在降低潜在毒性方面的优势。
