Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1
Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1
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DOI：
10.1056/nejmoa1904340
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发表时间：
2019-08-29
影响因子：
158.5
通讯作者：
Casa, C. Perez
中科院分区：
文献类型：
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作者：
Ayouba, A.;Butel, C.;Casa, C. Perez
背景以依法韦仑为基础的方案（600 mg剂量的依法韦仑，称为EFV 600）是世界卫生组织首选的人类免疫缺陷病毒1型（HIV-1）感染的一线治疗，直到2018年6月。考虑到副作用的关注，度鲁特韦为基础的和低剂量依法韦仑为基础的组合已被认为是HIV-1在资源有限的settings.MethodsWe进行了一项开放标签，多中心，随机，3期非劣效性试验在喀麦隆的一线治疗。未接受过抗逆转录病毒治疗且HIV-1 RNA水平（病毒载量）至少为1000拷贝/毫升的HIV-1感染成人被随机分配接受度鲁特韦或低剂量依法韦仑（400 mg剂量，称为EFV 400）的参考治疗，联合替诺福韦和拉米夫定。主要终点是根据美国食品和药物管理局的快照算法，在第48周时病毒载量低于50拷贝/毫升的参与者比例。治疗组之间的差异进行了计算，非劣效性进行了测试，利润率为10个百分点。ResultsA共613名参与者接受至少一个剂量的分配方案。在第48周，310名参与者中有231人的病毒载量低于每毫升50拷贝（74.5%），303名参与者中有209名EFV 400组为69.0%，差异为5.5个百分点（95%置信区间[CI]，-1.6至12.7; P1000拷贝/毫升）在度鲁特韦组的3名参与者（没有获得耐药突变）和EFV 400组的16名参与者中观察到。在度鲁特韦组中观察到比EFV 400组更多的体重增加（中位体重增加，5.0公斤与3.0公斤;肥胖症的发病率，12.3%与5.4%）。ConclusionsIn HIV-1感染的成人在喀麦隆，度鲁特韦为基础的方案是不劣于EFV 400为基础的参考方案在第48周的病毒抑制。在开始抗逆转录病毒治疗时病毒载量至少为每毫升10万拷贝的参与者中，病毒抑制的参与者比预期的要少。
BackgroundAn 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.MethodsWe 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.ResultsA 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; P1000 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%).ConclusionsIn 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.