Wyles David, Saag Michael, Viani Rolando M, Lalezari Jacob, Adeyemi Oluwatoyin, Bhatti Laveeza, Khatri Amit, King Jennifer R, Hu Yiran B, Trinh Roger, Shulman Nancy S, Ruane Peter
University of Colorado School of Medicine, Denver, USA.
Center for AIDS Research, University of Alabama, Birmingham, USA.
J Infect Dis. 2017 Feb 15;215(4):599-605. doi: 10.1093/infdis/jiw597.
Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART).
Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks.
Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment.
HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent.
ombitasvir/paritaprevir/ritonavir联合达沙布韦(OBV/PTV/r + DSV)±利巴韦林(RBV)已被批准用于治疗合并感染人类免疫缺陷病毒1型(HIV-1)的丙型肝炎病毒(HCV)基因1型(GT1)患者。在健康对照者中,同时给予OBV/PTV/r + DSV + 达芦那韦(DRV)会降低DRV的谷浓度(Ctrough)水平。为评估这一变化的临床意义,TURQUOISE-I研究的1b部分评估了在接受稳定的含DRV抗逆转录病毒疗法(ART)的合并感染患者中,OBV/PTV/r + DSV + RBV的疗效和安全性。
患者既往未接受过HCV治疗或曾接受过干扰素治疗,筛选时CD4 + 淋巴细胞计数≥200个细胞/µL或≥14%,且血浆HIV-1 RNA在每日一次(QD)含DRV的ART治疗下得到抑制。患者被随机分为维持每日800 mg DRV QD或换用每日两次(BID)600 mg DRV;所有患者均接受OBV/PTV/r + DSV + RBV治疗12周。
22例患者入组并实现了12周持续病毒学应答(SVR12)。无不良事件导致停药。联合用药对DRV的最大观察血浆浓度和曲线下面积影响极小;DRV QD和BID时的DRV Ctrough水平略低。治疗期间无患者的血浆HIV-1 RNA>200拷贝/mL。
接受稳定的含DRV ART治疗的HCV GT1/HIV-1合并感染患者实现了100%的SVR12,同时维持了血浆HIV-1 RNA抑制。尽管DRV暴露有所变化,但间歇性HIV-1病毒血症发作并不常见。