Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), Paris, France.
INSERM-TRANSFERT, Paris, France.
J Antimicrob Chemother. 2019 Nov 1;74(11):3305-3314. doi: 10.1093/jac/dkz338.
We assessed virological outcomes of darunavir use in France from 2012 to 2016, in three groups of people living with HIV (PLHIV): (i) antiretroviral (ARV)-naive PLHIV; (ii) ARV-experienced PLHIV switching to darunavir while failing therapy; and (iii) ARV-experienced PLHIV switching to darunavir while virologically controlled.
Virological success (VS) was defined as a plasma HIV-1 viral load (VL) <50 copies/mL and virological failure (VF) as two consecutive VL >50 copies/mL or one VL >50 copies/mL followed by a treatment switch prior to the next VL measurement. The cumulative incidence of VS was assessed considering darunavir discontinuation, loss to follow-up and death as competing risks, while estimates of cumulative incidence of VF accounted for loss to follow-up and death.
Among the 3235 ARV-naive PLHIV initiating darunavir, the 4 year cumulative incidence of VS was 80.9% and was associated with lower VL and higher CD4 cell counts. Among the 3485 ARV-experienced PLHIV switching to darunavir while failing therapy, the 4 year cumulative incidence of VS was 82.2% and was associated with lower VL. Among the 3005 ARV-experienced PLHIV switching to darunavir while virologically controlled, the 4 year cumulative incidence of VF was 12.6%. The risk of VF was higher with darunavir monotherapy [subdistribution hazard ratio (sHR)=1.67, 95% CI 1.15-2.42] while no difference was observed with dual therapy (sHR = 1.00, 95% CI 0.71-1.42) relative to triple therapy or more.
Darunavir-containing regimens yielded similarly high rates of viral suppression in PLHIV whether they were ARV naive or ARV experienced switching to darunavir while failing therapy, or of maintaining VS in ARV-experienced PLHIV switching to darunavir while virologically controlled.
我们评估了 2012 年至 2016 年期间法国使用达芦那韦的病毒学结果，研究对象为三组艾滋病毒感染者（PLHIV）：（i）未接受过抗逆转录病毒（ARV）治疗的 PLHIV；（ii）正在接受 ARV 治疗但治疗失败而转为达芦那韦治疗的 PLHIV；（iii）正在接受 ARV 治疗但病毒学控制良好而转为达芦那韦治疗的 PLHIV。
病毒学成功（VS）定义为血浆 HIV-1 病毒载量（VL）<50 拷贝/mL，病毒学失败（VF）定义为两次连续 VL>50 拷贝/mL 或一次 VL>50 拷贝/mL 后，在下一次 VL 测量之前进行治疗转换。达芦那韦停药、失访和死亡作为竞争风险，考虑到这些因素，评估了 VS 的累积发生率，而 VF 的累积发生率则考虑了失访和死亡因素。
在 3235 名接受 ARV 治疗的初治 PLHIV 中，达芦那韦治疗 4 年的累积 VS 发生率为 80.9%，与较低的 VL 和较高的 CD4 细胞计数相关。在 3485 名正在接受 ARV 治疗但治疗失败而转为达芦那韦治疗的 PLHIV 中，达芦那韦治疗 4 年的累积 VS 发生率为 82.2%，与较低的 VL 相关。在 3005 名正在接受 ARV 治疗且病毒学控制良好而转为达芦那韦治疗的 PLHIV 中，达芦那韦治疗 4 年的累积 VF 发生率为 12.6%。与三联或更多药物治疗相比，达芦那韦单药治疗的 VF 风险更高（亚分布危险比（sHR）=1.67，95%CI 1.15-2.42），而与双药治疗（sHR=1.00，95%CI 0.71-1.42）相比，风险无差异。
无论 PLHIV 是否为 ARV 初治或 ARV 经治失败转为达芦那韦治疗，或是正在接受 ARV 治疗且病毒学控制良好的 PLHIV 转为达芦那韦治疗，含达芦那韦的方案均能获得相似的高病毒抑制率。
