Young Jim, Scherrer Alexandra U, Calmy Alexandra, Tarr Philip E, Bernasconi Enos, Cavassini Matthias, Hachfeld Anna, Vernazza Pietro, Günthard Huldrych F, Bucher Heiner C
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerland.
Antivir Ther. 2019;24(5):343-353. doi: 10.3851/IMP3310.
Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) cause side effects in some patients, prompting the use of either partly or fully NRTI-sparing regimens.
We used data from the Swiss HIV Cohort Study to estimate the effectiveness of two new dolutegravir dual regimens relative to the alternative NRTI-sparing dual regimens that our clinicians used previously. We emulated two trials by propensity score matching case patients on the dolutegravir regimen with control patients on an alternative regimen. We analysed the case control sets using a Bayesian Cox model and estimated effectiveness as the percentage still on their trial regimen without virological failure at 48 weeks.
In a comparison of partly NRTI-sparing regimens, 58 cases treated with dolutegravir were matched to 17 controls treated with boosted darunavir (both with lamivudine or emtricitabine). The estimated difference in effectiveness was 15% (95% credible interval [CrI] 2-33) and 12% (95% CrI 0-26) in two sequential analyses 1 year apart. In a comparison of fully NRTI-sparing regimens, 54 cases treated with dolutegravir were matched to 32 controls treated with raltegravir (both with boosted darunavir). The estimated difference in effectiveness was 9% (95% CrI -1-21) and 5% (95% CrI -4-15) in the two sequential analyses.
Estimates of relative effectiveness suggest that both dolutegravir regimens are not inferior to these alternative regimens. All four regimens seem suitable for patients needing an NRTI-sparing regimen: there were few virological failures and few treatment changes due to toxicity.
核苷（或核苷酸）逆转录酶抑制剂（NRTIs）在一些患者中会引起副作用，这促使人们使用部分或完全不含NRTIs的方案。
我们利用瑞士HIV队列研究的数据，来评估两种新的多替拉韦双药方案相对于我们的临床医生之前使用的不含NRTIs的替代双药方案的有效性。我们通过倾向评分匹配，将接受多替拉韦方案治疗的病例患者与接受替代方案治疗的对照患者进行匹配，模拟了两项试验。我们使用贝叶斯Cox模型分析病例对照集，并将有效性估计为在48周时仍采用试验方案且无病毒学失败的患者百分比。
在部分不含NRTIs方案的比较中，58例接受多替拉韦治疗的病例与17例接受增强型达芦那韦治疗的对照患者（均联合拉米夫定或恩曲他滨）相匹配。在相隔1年的两次连续分析中，有效性估计差异分别为15%（95%可信区间[CrI] 2 - 33）和12%（95% CrI 0 - 26）。在完全不含NRTIs方案的比较中，54例接受多替拉韦治疗的病例与32例接受拉替拉韦治疗的对照患者（均联合增强型达芦那韦）相匹配。在两次连续分析中，有效性估计差异分别为9%（95% CrI -1 - 21）和5%（95% CrI -4 - 15）。
相对有效性估计表明，两种多替拉韦方案均不劣于这些替代方案。所有四种方案似乎都适合需要不含NRTIs方案的患者：病毒学失败很少，因毒性导致的治疗改变也很少。
