Gianotti Nicola, Poli Andrea, Galli Laura, Franzin Michela, Tadini Patrizia, Galizzi Nadia, Carbone Alessia, Merli Marco, Muccini Camilla, Oltolini Chiara, Andolina Andrea, Spagnuolo Vincenzo, Lazzarin Adriano, Castagna Antonella
Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.
Pharmacy, San Raffaele Scientific Institute, Milano, Italy.
PLoS One. 2017 Aug 1;12(8):e0182007. doi: 10.1371/journal.pone.0182007. eCollection 2017.
Aim of this study was to evaluate the efficacy and the safety of switching from branded to generic antiretrovirals in patients with HIV-RNA <50 copies/mL.
Matched-cohort study of patients followed at a single clinical center. Since September 2014, all patients with HIV-RNA <50 copies/mL who were receiving branded lamivudine or zidovudine/lamivudine or efavirenz were switched to the generic compound (switchers) and matched, in a ratio 1:1, for age (±5 years), gender, anti-HCV antibodies, nadir and (±50 cells/μL) baseline CD4+ count (±100 cells/μL), duration of antiretroviral therapy (±1 year), with patients with HIV-RNA <50 copies/mL, on treatment with unavailable generic compounds (non-switchers). Incidence rates (IR) of different outcomes were calculated and compared by Poisson regression model. A confirmed HIV-RNA ≥50 copies/mL defined virological failure; any change in the antiretroviral regimen was defined as treatment discontinuation.
Four hundred forty patients were switched to generic compounds (268 [61%] on lamivudine, 65 [15%] on zidovudine/lamivudine, 87 [20%] on efavirenz and 20 [4%] on efavirenz and either lamivudine or zidovudine/lamivudine). Over a median follow-up of 15.0 (12.1-15.7) months, virological failure occurred in four switchers (IR: 0.07 [0.02-0.18]/100-person months of follow-up [PMFU]) and in ten non-switchers (IR: 0.20 [0.10-0.35]/100-PMFU) (p = 0.0003), while treatment discontinuation occurred in 118 switchers (IR: 2.05 [1.70-2.44]/100-PMFU) and in 128 non-switchers (IR: 2.37 [1.99-2.81]/100-PMFU) (p = 0.699).
After more than one year of follow-up, we found no evidence of increased risk of reduced efficacy or increased toxicity after switching from branded to generic lamivudine or zidovudine/lamivudine or efavirenz.
本研究的目的是评估HIV-RNA＜50拷贝/毫升的患者从品牌抗逆转录病毒药物转换为通用型抗逆转录病毒药物的疗效和安全性。
在单一临床中心对患者进行配对队列研究。自2014年9月起，所有HIV-RNA＜50拷贝/毫升且正在接受品牌拉米夫定、齐多夫定/拉米夫定或依非韦伦治疗的患者转换为通用型复方制剂（转换组），并按照年龄（±5岁）、性别、抗丙型肝炎病毒抗体、最低点和（±50个细胞/微升）基线CD4+细胞计数（±100个细胞/微升）、抗逆转录病毒治疗持续时间（±1年）以1:1的比例与HIV-RNA＜50拷贝/毫升且正在接受无法获得的通用型复方制剂治疗的患者（非转换组）进行配对。通过泊松回归模型计算并比较不同结局的发生率（IR）。HIV-RNA≥50拷贝/毫升确诊为病毒学失败；抗逆转录病毒治疗方案的任何改变定义为治疗中断。
440例患者转换为通用型复方制剂（268例[61%]接受拉米夫定，65例[15%]接受齐多夫定/拉米夫定，87例[20%]接受依非韦伦，20例[4%]接受依非韦伦联合拉米夫定或齐多夫定/拉米夫定）。在中位随访15.0（12.1-15.7）个月期间，4例转换组患者发生病毒学失败（IR：0.07[0.02-0.18]/100人月随访[PMFU]），10例非转换组患者发生病毒学失败（IR：0.20[0.10-0.35]/100-PMFU）（p=0.0003），而118例转换组患者发生治疗中断（IR：2.05[1.70-2.44]/100-PMFU），128例非转换组患者发生治疗中断（IR：2.37[1.99-2.81]/100-PMFU）（p=0.699）。
经过一年多的随访，我们没有发现从品牌拉米夫定、齐多夫定/拉米夫定或依非韦伦转换为通用型药物后疗效降低或毒性增加风险升高的证据。
