法国蒙彼利埃大学Eric Delaporte小组的一项最新研究分析了基于Dolutegravir或低剂量依法韦仑治疗HIV-1的方案。 2019年8月29日，国际知名学术期刊《新英格兰医学杂志》发表了这一成果。

该课题组研究人员在喀麦隆进行了一项开放标签、多中心、随机、临床3期的非劣效性试验。613名参与者均为未接受抗逆转录病毒治疗且HIV-1 RNA水平超过1000拷贝/毫升的成年人，他们被随机分配接受Dolutegravir治疗（Dolutegravir组，301名）或低剂量依法韦伦的参考治疗（400毫克剂量，EFV400组，303名），同时联用泰诺福韦和拉米夫定。

第48周，Dolutegravir组中231名（74.5%）受试者的病毒载量低于50拷贝/毫升，而EFV400组中有209名（69.0%），差异为5.5个百分点；DoluteGravir组中207名基线病毒载量超过100000拷贝/毫升的患者中有137名（66.2%）最终病毒载量低于50拷贝/毫升，而EFV400组200名中有123名（61.5%），差异为4.7个百分点。

Dolutegravir组中有3名受试者病毒治疗失败（最终病毒载量大于1000拷贝/毫升），EFV400组中有16名。Dolutegravir组的中位体重增加为5.0 kg，肥胖发生率为12.3%；EFV400组中位体重增加3.0 kg，肥胖发生率为5.4%。
在喀麦隆感染HIV-1的成年人中，Dolutegravir方案在第48周时的病毒抑制效果并不逊于EFV400参考方案。 但对于病毒载量超过100000拷贝/毫升的患者而言，病毒抑制的效果比预期要差。

据悉，在2018年6月以前，世界卫生组织首选依法韦仑600毫克（EFV600）来一线治疗人类免疫缺陷病毒1型（HIV-1）感染。考虑到其副作用，在资源有限的背景下，基于Dolutegravir和低剂量依法韦仑的联合方案可用于HIV-1的一线治疗。 

附：英文原文

Title: Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1

Author: The NAMSAL ANRS 12313 Study Group*

Issue&Volume: Vol 381 No 9, 29 August 2019

Abstract: 

BACKGROUND
An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz–based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings.

METHODS
We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points.

RESULTS
A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], −1.6 to 12.7; P<0.001 for noninferiority). Among those with a baseline viral load of at least 100,000 copies per milliliter, a viral load of less than 50 copies per milliliter was observed in 137 of 207 participants (66.2%) in the dolutegravir group and in 123 of 200 participants (61.5%) in the EFV400 group, with a difference of 4.7 percentage points (95% CI, −4.6 to 14.0). Virologic failure (a viral load of >1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%).

CONCLUSIONS
In HIV-1–infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.)

DOI: 10.1056/NEJMoa1904340

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1904340