在资源有限的环境下，用艾维雷韦、考比司他、恩曲他滨和替诺福韦富马酸酯单片复方制剂治疗人类免疫缺陷病毒 2 型感染的初治方案的试验：来自塞内加尔，西非的 48 周结果。
A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa.
机构信息
Service des Maladies Infectieuses et Tropicales Ibrahima Diop Mar, Centre Hospitalier National Universitaire de Fann, Universite Cheikh Anta Diop de Dakar, Senegal; and Departments of.
Medicine.
出版信息
Clin Infect Dis. 2018 Oct 30;67(10):1588-1594. doi: 10.1093/cid/ciy324.
BACKGROUND
There is an urgent need for safe and effective antiretroviral therapy (ART) for human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals in Senegal, West Africa.
METHODS
HIV-2-infected, ART-naive adults with World Health Organization stage 3-4 disease or CD4 count <750 cells/μL were eligible for this 48-week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality, and loss to follow-up.
RESULTS
We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and 1 loss to follow-up. The median baseline CD4 count was 408 (range, 34-747) cells/μL, which increased by a median 161 (range, 27-547) cells/μL at week 48. Twenty-five subjects had baseline HIV-2 VL of <50 copies/mL of plasma. In those with detectable HIV-2 VL, the median was 41 (range, 10-6135) copies/mL. Using a modified intent-to-treat analysis (US Food and Drug Administration Snapshot method), 28 of 30 (93.3%; 95% confidence interval, 77.9%-99.2%) had viral suppression at 48 weeks. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. There were 8 grade 3-4 adverse events; none were deemed study related. Adherence and acceptability were good.
CONCLUSIONS
Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well tolerated. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment.
CLINICAL TRIALS REGISTRATION
NCT02180438.
背景
目前迫切需要安全有效的抗逆转录病毒疗法（ART）来治疗人类免疫缺陷病毒 2 型（HIV-2）感染。我们在西非塞内加尔进行了首次含有艾维雷格、考比司他、恩曲他滨和替诺福韦艾拉酚胺富马酸盐（E/C/F/TDF）的单片方案治疗 HIV-2 感染者的临床试验，以评估其在该人群中的疗效。
方法
患有 HIV-2 且未接受过 ART 的成年人，若符合世界卫生组织（WHO）分期 3-4 期疾病或 CD4 计数<750 个细胞/μL，则有资格参加本项 48 周的开放性临床试验。我们对 HIV-2 病毒载量（VL）、CD4 计数、临床和不良事件、死亡率和失访进行了分析。
结果
我们纳入了 30 名开始接受 E/C/F/TDF 治疗的 HIV-2 感染、未接受过 ART 的成年人。29 名受试者完成了 48 周的随访。其中大多数为女性（80%）。无死亡、新的 AIDS 相关临床事件和 1 例失访。基线时 CD4 计数中位数为 408（范围，34-747）个细胞/μL，在第 48 周时增加了中位数 161（范围，27-547）个细胞/μL。25 名受试者基线时 HIV-2 VL<50 拷贝/mL 的血浆。在那些 HIV-2 VL 可检测到的患者中，中位数为 41（范围，10-6135）拷贝/mL。采用修改后的意向治疗分析（美国食品药品监督管理局快照方法），30 名受试者中 28 名（93.3%；95%置信区间，77.9%-99.2%）在第 48 周时病毒得到抑制。1 名病毒学失败的患者在第 48 周检测到 HIV-2 对多种药物具有耐药性（逆转录酶突变：K65R；整合酶突变：G140S 和 Q148R）。有 8 例 3-4 级不良事件，均与研究无关。依从性和可接受性良好。
结论
我们的数据表明，每日 1 次、单片的 E/C/F/TDF 方案安全、有效且耐受性良好。我们的发现支持使用整合酶抑制剂为基础的方案治疗 HIV-2。
临床试验注册
NCT02180438。
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