Han Yang, Li Yijia, Xie Jing, Qiu Zhifeng, Li Yanling, Song Xiaojing, Zhu Ting, Li Taisheng
Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.
PLoS One. 2015 Mar 30;10(3):e0120705. doi: 10.1371/journal.pone.0120705. eCollection 2015.
Tenofovir (TDF) and ritonavir-boosted lopinavir (LPV/r) were not introduced to China as second-line medications until 2009. The efficacy and safety of TDF/3TC/LPV/r based second-line regimen have not been evaluated in Chinese HIV patients who failed first-line regimens.
This was a multicenter cohort study recruiting patients from Beijing, Shanghai, Guangdong, and Henan provinces between November 2008 and January 2010. Eighty HIV infected patients failing first-line regimens with serum creatinine lower than 1.5 times the upper limit of normal received TDF+ lamivudine (3TC)+ LPV/r were followed up for 120 weeks. CD4 cell count, viral load, and estimated glomerular filtration rate (eGFR) were monitored at each visit.
At baseline, 31.2% and 48.8% of patients had moderate/high-level resistance to TDF and 3TC, respectively; while 2.5% of patients had only low-level resistance to LPV/r. During 120 weeks of follow-up, virological suppression rate reached over 70% (<40 copies/ml) and 90% (<400 copies/ml), and median CD4 cell count increased from 157 cells/μL at baseline to 307 cells/μL at week 120. Baseline drug-resistance mutations had no impact on the efficacy of second-line antiretroviral therapy. Median eGFR dropped from 104.7 ml/min/1.73m2 at baseline to 95.6 ml/min/1.73m2 at week 24 and then recovered after week 96.
This study for the first time demonstrated that TDF+ 3TC+ LPV/r was efficacious as second-line regimen with acceptable nephrotoxicity profiles in patients who failed zidovudine or stavudine based first-line regimens in China.
ClinicalTrials.gov NCT00872417.
替诺福韦（TDF）和利托那韦增强型洛匹那韦（LPV/r）直到2009年才作为二线药物引入中国。基于TDF/3TC/LPV/r的二线治疗方案在中国一线治疗方案失败的HIV患者中的疗效和安全性尚未得到评估。
这是一项多中心队列研究，于2008年11月至2010年1月期间从北京、上海、广东和河南省招募患者。80例一线治疗方案失败且血清肌酐低于正常上限1.5倍的HIV感染患者接受TDF+拉米夫定（3TC）+LPV/r治疗，并随访120周。每次随访时监测CD4细胞计数、病毒载量和估计肾小球滤过率（eGFR）。
基线时，分别有31.2%和48.8%的患者对TDF和3TC有中度/高度耐药；而2.5%的患者仅对LPV/r有低度耐药。在120周的随访期间，病毒学抑制率达到70%以上（<40拷贝/ml）和90%以上（<400拷贝/ml），CD4细胞计数中位数从基线时的157个细胞/μL增加到第120周时的307个细胞/μL。基线耐药突变对二线抗逆转录病毒治疗的疗效没有影响。eGFR中位数从基线时的104.7 ml/min/1.73m²下降到第24周时的95.6 ml/min/1.73m²，然后在第96周后恢复。
本研究首次证明，在中国基于齐多夫定或司他夫定的一线治疗方案失败的患者中，TDF+3TC+LPV/r作为二线治疗方案有效，且肾毒性可接受。
ClinicalTrials.gov NCT00872417。
