Uemura Haruka, Tsukada Kunihisa, Mizushima Daisuke, Aoki Takahiro, Watanabe Koji, Kinai Ei, Teruya Katsuji, Gatanaga Hiroyuki, Kikuchi Yoshimi, Sugiyama Masaya, Mizokami Masashi, Oka Shinichi
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
PLoS One. 2017 Oct 18;12(10):e0186255. doi: 10.1371/journal.pone.0186255. eCollection 2017.
Almost 30 years ago, about 30% of Japanese hemophiliacs became infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated blood products. While several studies have reported the high efficacy and safety of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are limited in hemophiliacs.
We conducted a single-center, open-label study involving 27 Japanese patients (median age; 45 years) with inherited bleeding disorders who were co-infected with HCV/HIV-1. Patients with HCV genotype 1 (GT1) and GT4 received ledipasvir (90 mg) plus sofosbuvir (400 mg), those with HCV GT2 received sofosbuvir plus weight-based ribavirin, and those with HCV GT3 received daclatasvir (60 mg) plus sofosbuvir. Treatment was continued for 12 weeks in all patients. The primary endpoints were rate of sustained virologic response at 12 weeks after end of therapy (SVR12) and occurrence of adverse events during DAA therapy.
Eighteen (67%) patients had had received interferon-based therapy, and 11 (41%) had compensated cirrhosis. HCV genotypes were GT1a 4 (15%), GT1b 16 (59%), GT1 undetermined 2 (7%), GT2a 1 (4%), GT3a 3 (11%) and GT4a 1 (4%). All patients were on combination antiretroviral therapy (cART) and had undetectable HIV-1 viral load (<20 copies/μL) at baseline. All patients achieved SVR12. Serious adverse events were observed in 3 patients: arteritis of the leg, which resolved after completion of DAA therapy, asymptomatic QT prolongation and gastrointestinal hemorrhage. cART failure was noted in one patient due to emergence of raltegravir resistance during ledipasvir/sofosbuvir treatment. Although α-fetoprotein, Mac-2 binding protein glycosylation isomer (M2BPGi), and Fibro Scan (FS) scores decreased in most patients during DAA therapy, M2BPGi (>2.0 cutoff index) and FS scores (>15.0 kPa) were still high in 6 patients at week 36.
DAA therapy is effective in all patients. However, adverse events and efficacy of cART should be monitored closely.
大约30年前，约30%的日本血友病患者在接受受污染的血液制品后感染了HIV-1和丙型肝炎病毒（HCV）。虽然多项研究报告了直接抗病毒药物（DAA）在HIV-1合并感染患者中的高疗效和安全性，但血友病患者的此类数据有限。
我们进行了一项单中心、开放标签研究，纳入了27例合并感染HCV/HIV-1的日本遗传性出血性疾病患者（中位年龄45岁）。HCV基因1型（GT1）和GT4型患者接受来迪派韦（90毫克）加索磷布韦（400毫克）治疗，HCV GT2型患者接受索磷布韦加基于体重的利巴韦林治疗，HCV GT3型患者接受达卡他韦（60毫克）加索磷布韦治疗。所有患者均持续治疗12周。主要终点为治疗结束后12周的持续病毒学应答率（SVR12）以及DAA治疗期间不良事件的发生情况。
18例（67%）患者曾接受基于干扰素的治疗，11例（41%）有代偿期肝硬化。HCV基因型为GT1a 4例（15%）、GT1b 16例（59%）、GT1未确定2例（7%）、GT2a 1例（4%）、GT3a 3例（11%）和GT4a 1例（4%）。所有患者均接受抗逆转录病毒联合治疗（cART），且基线时HIV-1病毒载量不可检测（<20拷贝/微升）。所有患者均实现了SVR12。3例患者出现严重不良事件：腿部动脉炎，在DAA治疗完成后缓解；无症状QT延长；胃肠道出血。1例患者由于在来迪派韦/索磷布韦治疗期间出现拉替拉韦耐药而出现cART失败。虽然大多数患者在DAA治疗期间甲胎蛋白、Mac-2结合蛋白糖基化异构体（M2BPGi）和Fibro Scan（FS）评分下降，但在第36周时，6例患者的M2BPGi（临界指数>2.0）和FS评分（>15.0千帕）仍然较高。
DAA治疗对所有患者均有效。然而，应密切监测不良事件和cART的疗效。
