多替拉韦/拉米夫定在病毒学抑制的人类免疫缺陷病毒感染者中不劣于继续使用基于多替拉韦和非多替拉韦的三联抗逆转录病毒疗法：全国性前瞻性配对队列研究DUALING

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

作者信息

Vasylyev Marta, Wit Ferdinand W N M, Jordans Carlijn C E, Soetekouw Robin, van Lelyveld Steven F L, Kootstra Gert-Jan, Delsing Corine E, Ammerlaan Heidi S M, van Kasteren Marjo E E, Brouwer Annemarie E, Leyten Eliane M S, Claassen Mark A A, Hassing Robert-Jan, den Hollander Jan G, van den Berge Marcel, Roukens Anna H E, Bierman Wouter F W, Groeneveld Paul H P, Lowe Selwyn H, van Welzen Berend J, Richel Olivier, Nellen Jeannine F, van den Berk Guido E L, van der Valk Marc, Rijnders Bart J A, Rokx Casper

机构信息

Section of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.

Stichting HIV Monitoring, Amsterdam, The Netherlands.

出版信息

Open Forum Infect Dis. 2024 Mar 18;11(4):ofae160. doi: 10.1093/ofid/ofae160. eCollection 2024 Apr.

BACKGROUND

Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.

METHODS

Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4 T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin.

RESULTS

The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued.

CONCLUSIONS

In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.

CLINICAL TRIALS REGISTRATION

NCT04707326.

背景

在临床实践中证实多替拉韦/拉米夫定的疗效可巩固其使用建议。

方法

在荷兰24个人类免疫缺陷病毒（HIV）治疗中心开展前瞻性队列研究（DUALING）。HIV RNA得到抑制的病例采用三联抗逆转录病毒疗法，且既往无病毒学失败或耐药情况，开始使用多替拉韦/拉米夫定。病例与采用基于多替拉韦的疗法的三联抗逆转录病毒疗法对照组在年龄、性别、传播途径、CD4 T细胞最低点以及HIV RNA峰值方面按1:2进行匹配。主要终点是在意向性治疗和实际治疗分析中，1年后病例组与对照组的治疗失败率，非劣效界值为5%。

结果

2040名参与者中，病例组680例，对照组1380例。在意向性治疗分析中，390例基于多替拉韦的病例组与对照组的治疗失败率分别为8.72%和12.50%（差值：-3.78%[95%置信区间{CI}，-7.49%至0.08%]），在实际治疗分析中分别为1.39%和0.80%（差值：0.59%[95% CI，-0.80%至1.98%]）。290例非多替拉韦方案的病例的治疗失败风险也不劣于对照组。与病毒学失败无关的抗逆转录病毒疗法调整解释了意向性治疗分析中较高的治疗失败率。三联抗逆转录病毒治疗时间较短以及非西方血统与治疗失败相关。治疗失败定义为连续两次HIV RNA>50拷贝/mL，病例组4例，对照组5例，但未检测到基因型耐药。病例组和对照组的病毒波动情况相当，但病例组体重增加更多，尤其是停用基于替诺福韦的方案时。