解读观察性队列中两种药物治疗方案选择及变更的原因：基于利托那韦增强型蛋白酶抑制剂的一线治疗方案与基于非核苷类逆转录酶抑制剂的一线治疗方案的比较

Interpreting the reasons for the choice and changing of two drug regimens in an observational cohort: comparison of a ritonavir-boosted protease inhibitor-based versus a nonnucleoside reverse transcriptase inhibitor-based first-line regimen.

作者信息

Jarrin I, Hernández-Novoa B, Alejos B, Santos I, Lopez-Aldeguer J, Riera M, Gutiérrez F, Rubio R, Antela A, Blanco J R, Moreno S

机构信息

Institute of Health Carlos III, Madrid, Spain.

出版信息

HIV Med. 2014 Oct;15(9):547-56. doi: 10.1111/hiv.12144. Epub 2014 Mar 24.

DOI:10.1111/hiv.12144

PMID:24655804

Abstract

OBJECTIVES

We compared reasons for the choice of regimen, time to and reasons for third drug modification, virological response and change in CD4 T-cell counts in patients started on atazanavir/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line regimens.

METHODS

We included patients from the Cohort of the Spanish HIV Research Network (CoRIS), a multicentre cohort of HIV-positive treatment-naïve subjects, in the study. We used logistic regression to assess factors associated with choosing ATV/r vs. EFV, proportional hazards models on the subdistribution hazard to estimate subdistribution hazard ratios (sHRs) for third drug modification, logistic regression to estimate odds ratios (ORs) for virological response and linear regression to assess mean differences in CD4 T-cell count increase from baseline.

RESULTS

Of 2167 patients, 10.7% started on ATV/r. ATV/r was more likely than EFV to be prescribed in injecting drug users [adjusted OR 1.85; 95% confidence interval (CI) 1.03-3.33], in 2009-2010 (adjusted OR 1.63; 95% CI 1.08-2.47) and combined with abacavir plus lamivudine (adjusted OR 1.53; 95% CI 0.98-2.43). Multivariate analyses showed no differences, comparing ATV/r vs. EFV, in the risk of third drug modification (sHR 1.04; 95% CI 0.74-1.46) or in virological response (OR 0.81; 95% CI 0.46-1.41); differences in mean CD4 T-cell count increase from baseline were at the limit of statistical significance (mean difference 29.8 cells/μL; 95% CI -4.1 to 63.6 cells/μL). In patients changing from EFV, 48% of changes were attributable to toxicity/adverse events, 16% to treatment failure/resistance, 3% to simplification, and 8 and 12%, respectively, to patients' and physicians' decisions; these percentages were 24, 6, 12, 14 and 24%, respectively, in those changing from ATV/r.

CONCLUSIONS

ATV/r- and EFV-based regimens meet the requirements of both efficacy and safety for initial combination antiretroviral regimen, which relate to better durability.

摘要

目的

我们比较了接受基于阿扎那韦/利托那韦（ATV/r）与基于依非韦伦（EFV）的一线治疗方案的患者在选择治疗方案的原因、第三次药物调整的时间及原因、病毒学反应以及CD4 T细胞计数变化方面的差异。

方法

我们纳入了西班牙HIV研究网络队列（CoRIS）中的患者，这是一个针对未接受过治疗的HIV阳性受试者的多中心队列。我们使用逻辑回归来评估与选择ATV/r vs. EFV相关的因素，使用亚分布风险的比例风险模型来估计第三次药物调整的亚分布风险比（sHRs），使用逻辑回归来估计病毒学反应的比值比（ORs），并使用线性回归来评估CD4 T细胞计数相对于基线增加的平均差异。

结果

在2167例患者中，10.7%开始接受ATV/r治疗。在注射吸毒者中，ATV/r比EFV更有可能被处方[调整后的OR为1.85；95%置信区间（CI）为1.03 - 3.33]，在2009 - 2010年（调整后的OR为1.63；95% CI为1.08 - 2.47），并且与阿巴卡韦加拉米夫定联合使用时（调整后的OR为1.53；95% CI为0.98 - 2.43）。多变量分析显示，比较ATV/r与EFV，在第三次药物调整的风险（sHR为1.04；95% CI为0.74 - 1.46）或病毒学反应（OR为0.81；95% CI为0.46 - 1.41）方面没有差异；相对于基线，CD4 T细胞计数增加的平均差异处于统计学意义的临界值（平均差异为29.8个细胞/μL；95% CI为 - 4.1至63.6个细胞/μL）。在从EFV转换治疗的患者中，48%的转换归因于毒性/不良事件，16%归因于治疗失败/耐药，3%归因于简化治疗，分别有8%和12%归因于患者和医生的决定；在从ATV/r转换治疗的患者中，这些百分比分别为24%、6%、12%、14%和24%。