Kanters Steve, Vitoria Marco, Zoratti Michael, Doherty Meg, Penazzato Martina, Rangaraj Ajay, Ford Nathan, Thorlund Kristian, Anis Prof Aslam H, Karim Mohammad Ehsanul, Mofenson Lynne, Zash Rebecca, Calmy Alexandra, Kredo Tamara, Bansback Nick
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
Department of HIV/AIDS, WHO, Geneva, Switzerland.
EClinicalMedicine. 2020 Oct 16;28:100573. doi: 10.1016/j.eclinm.2020.100573. eCollection 2020 Nov.
To inform World Health Organization (WHO) global guidelines, we updated and expanded the evidence base to assess the comparative efficacy, tolerability, and safety of first-line antiretroviral therapy (ART) regimens.
We searched Embase, Medline and CENTRAL on 28 February 2020 to update the systematic literature review of clinical trials comparing recommended first-line ART that informed previous WHO guidelines. Outcomes included viral suppression, change in CD4 cell counts, mortality, serious and overall adverse events (AEs), discontinuation, discontinuations due to AEs (DAEs); and new outcomes: drug-resistance, neuropsychiatric AEs, early viral suppression, weight gain and birth outcomes. Comparative effects were assessed through network meta-analyses and certainty in the evidence was assessed using the GRADE framework.
We identified 156 publications pertaining to 68 trials for the primary population. Relative to efavirenz, dolutegravir had improved odds of viral suppression across all time points (odds ratio [OR]: 1·94; 95% credible interval [CrI]: 1·48-2·56 at 96 weeks); was protective of drug-resistance (OR: 0·13; 95%CrI: 0·04-0·48); and led to fewer discontinuations (OR: 0·58; 95%CrI: 0·48-0·70). Evidence supported dolutegravir use among TB-HIV co-infected persons and pregnant women. Adverse birth outcomes were observed in 33.2% of dolutegravir-managed pregnancies and 35.0% of efavirenz-managed pregnancies. Low-dose efavirenz had comparable efficacy and safety to standard-dose efavirenz, but led to fewer DAEs (OR: 0·70; 95%CrI: 0·50-0·92).
The evidence supports choosing dolutegravir in combination with lamivudine/emtricitabine and tenofovir disoproxil fumarate as the preferred first-line regimen and low-dose efavirenz-based regimens as an alternative. Dolutegravir can be considered to be effective, safe and tolerable.
WHO.
为给世界卫生组织（WHO）全球指南提供信息，我们更新并扩充了证据库，以评估一线抗逆转录病毒疗法（ART）方案的相对疗效、耐受性和安全性。
我们于2020年2月28日检索了Embase、Medline和CENTRAL数据库，以更新对比较推荐的一线ART的临床试验的系统文献综述，该综述为之前的WHO指南提供了依据。结局包括病毒抑制、CD4细胞计数变化、死亡率、严重及总体不良事件（AE）、停药、因AE导致的停药（DAE）；以及新的结局：耐药性、神经精神AE、早期病毒抑制、体重增加和出生结局。通过网状荟萃分析评估比较效果，并使用GRADE框架评估证据的确定性。
我们确定了156篇与针对主要人群的68项试验相关的出版物。相对于依非韦伦，多替拉韦在所有时间点的病毒抑制几率均有所提高（优势比[OR]：1.94；95%可信区间[CrI]：在96周时为1.48 - 2.56）；具有抗耐药性（OR：0.13；95%CrI：0.04 - 0.48）；且导致停药的情况较少（OR：0.58；95%CrI：0.48 - 0.70）。有证据支持在结核合并艾滋病毒感染患者和孕妇中使用多替拉韦。在接受多替拉韦治疗的妊娠中，33.2%出现不良出生结局，在接受依非韦伦治疗的妊娠中，这一比例为35.0%。低剂量依非韦伦的疗效和安全性与标准剂量依非韦伦相当，但导致的DAE较少（OR：0.70；95%CrI：0.50 - 0.92）。
证据支持选择多替拉韦联合拉米夫定/恩曲他滨和替诺福韦酯作为首选一线方案，以及以低剂量依非韦伦为基础的方案作为替代方案。多替拉韦可被认为是有效、安全且耐受性良好的。
WHO。
