Galizzi Nadia, Galli Laura, Poli Andrea, Gianotti Nicola, Carini Elisabetta, Bigoloni Alba, Tambussi Giuseppe, Nozza Silvia, Lazzarin Adriano, Castagna Antonella, Mancusi Daniela, Termini Roberta
Infectious Diseases, IRCCS San Raffaele, Milan, Italy.
Università Vita-Salute San Raffaele, Milan, Italy.
PLoS One. 2018 Feb 16;13(2):e0191300. doi: 10.1371/journal.pone.0191300. eCollection 2018.
A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen.
Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015. The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters.
In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient's decision, 1 due to enrolment in a study protocol].
In this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.
含利匹韦林（RPV）、阿巴卡韦（ABC）和拉米夫定（3TC）的治疗方案简单，且可能无需使用替诺福韦和蛋白酶抑制剂。然而，关于将此联合用药作为换药策略的数据有限。本研究的目的是评估该治疗方案的长期疗效和安全性。
对2013年3月至2015年9月在圣拉斐尔科学研究所传染病科接受随访的HIV-1感染患者进行回顾性研究，这些患者HBsAg阴性、HLA B5701阴性，对RPV、ABC和3TC无耐药记录，HIV-RNA<50拷贝/mL，开始使用RPV加ABC/3TC治疗。主要结局是治疗持久性[无治疗失败（TF）]。次要目标是评估免疫、代谢和其他安全性参数的变化。TF定义为病毒学失败（VF，连续两次值>50拷贝/mL）或因任何原因停用治疗方案中的任何药物。患者随访从开始使用RPV加ABC/3TC之日起，至发生TF（VF或停用治疗方案中的任何药物）或最后一次可获得访视之日。通过Kaplan-Meier曲线评估至TF的时间。应用混合线性模型评估免疫、代谢和其他安全性参数的变化。
在本分析中，纳入了100例开始使用RPV加ABC/3TC的患者。转换至RPV加ABC/3TC后12、24和36个月时未发生TF的患者比例分别为88%[95%置信区间（CI）：79%-93%]、82%（95%CI：73%-89%）和78%（95%CI：68%-86%）。至TF的时间未受到CD4+最低点（≤200 vs>200细胞/μl；对数秩检验：p = 0.311）或ART前病毒载量（<100000 vs≥100000拷贝/mL；对数秩检验：p = 0.574）或既往抗逆转录病毒治疗方案类型（PI+2NRTIs vs NNRTI+2NRTIs vs其他；对数秩检验：p = 0.942）显著影响。在中位随访2.9年（四分位间距：1.9-3.5）期间，26例患者停止治疗[10例因毒性，7例因与其他药物相互作用，3例因心血管风险担忧，2例因单次病毒波动，1例因VF，1例因哮喘，1例患者决定，1例因参加研究方案]。
在本回顾性研究中，长期使用RPV加ABC/3TC治疗方案有效且安全。未发现该治疗方案的疗效受低CD4+最低点或高ART前病毒载量影响。
