Swartz J E, Vandekerckhove L, Ammerlaan H, de Vries A C, Begovac J, Bierman W F W, Boucher C A B, van der Ende M E, Grossman Z, Kaiser R, Levy I, Mudrikova T, Paredes R, Perez-Bercoff D, Pronk M, Richter C, Schmit J C, Vercauteren J, Zazzi M, Židovec Lepej S, De Luca A, Wensing A M J
Department of Medical Microbiology, Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of General Internal Medicine, Ghent University, Ghent, Belgium.
J Antimicrob Chemother. 2015;70(6):1850-7. doi: 10.1093/jac/dkv033. Epub 2015 Mar 3.
The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice.
A multicentre cohort study was performed in therapy-naive patients initiating ART with TELE before July 2009. Efficacy was studied using ITT (missing or switch = failure) and on-treatment (OT) analyses. Genotypic susceptibility scores (GSSs) were determined using the Stanford HIVdb algorithm.
Efficacy analysis of 1608 patients showed virological suppression to <50 copies/mL at 48 weeks in 91.5% (OT) and 70.6% (ITT). Almost a quarter of all patients (22.9%) had discontinued TELE at week 48, mainly due to CNS toxicity. Virological failure within 48 weeks was rarely observed (3.3%, n = 53). In multilevel, multivariate analysis, infection with subtype B (P = 0.011), baseline CD4 count <200 cells/mm³ (P < 0.001), GSS <3 (P = 0.002) and use of lamivudine (P < 0.001) were associated with a higher risk of virological failure. After exclusion of patients using co-formulated compounds, virological failure was still more often observed with lamivudine. Following virological failure, three-quarters of patients switched to a PI-based regimen with GSS <3. After 1 year of second-line therapy, viral load was suppressed to <50 copies/mL in 73.5% (OT).
In clinical practice, treatment failure on TELE regimens is relatively frequent due to toxicity. Virological failure is rare and more often observed with lamivudine than with emtricitabine. Following virological failure on TELE, PI-based second-line therapy was often successful despite GSS <3.
替诺福韦与依法韦仑联合拉米夫定或恩曲他滨（TELE）在一线治疗HIV-1感染的临床试验中已被证明具有高效性。然而，关于其在常规临床实践中的疗效数据有限。
对2009年7月前开始接受TELE抗逆转录病毒治疗的初治患者进行了一项多中心队列研究。使用意向性分析（ITT，缺失或换药=治疗失败）和治疗中分析（OT）来研究疗效。使用斯坦福HIVdb算法确定基因型易感性评分（GSS）。
对1608例患者的疗效分析显示，在48周时，91.5%（OT）和70.6%（ITT）的患者病毒学抑制至<50拷贝/毫升。在48周时，几乎四分之一（22.9%）的患者停用了TELE，主要原因是中枢神经系统毒性。48周内很少观察到病毒学失败（3.3%，n = 53）。在多水平、多变量分析中，B亚型感染（P = 0.011）、基线CD4细胞计数<200个/立方毫米（P < 0.001）、GSS<3（P = 0.002）和使用拉米夫定（P < 0.001）与病毒学失败风险较高相关。在排除使用复方制剂的患者后，拉米夫定组仍更常观察到病毒学失败。病毒学失败后，四分之三的患者换用了基于蛋白酶抑制剂的方案，GSS<3。二线治疗1年后,73.5%（OT）的患者病毒载量抑制至<50拷贝/毫升。
在临床实践中，由于毒性，TELE方案的治疗失败相对常见。病毒学失败很少见，拉米夫定组比恩曲他滨组更常观察到。TELE治疗出现病毒学失败后，尽管GSS<3，但基于蛋白酶抑制剂的二线治疗通常成功。
