含替诺福韦与克力芝的HAART方案对HIV/AIDS病人肾功能的影响

Impact of tenofovir disoproxil fumarate plus lopinavir/ritonavir based on highly active antiretroviral therapy regimens on renal function in HIV/AIDS patients

目的评价含替诺福韦(TDF)与克力芝(LPV/r)方案的高效抗反转录病毒治疗(HAART)方案,对艾滋病(HIV/AIDS)病人肾功能的影响。方法 75例一线抗病毒治疗失败接受二线方案治疗(TDF组:TDF+LPV/r+3TC)的HIV/AIDS病人,以及1∶1匹配的初治HIV/AIDS病人(对照组:D4T/AZT+NVP+3TC),检测基线及48周时的CD4T淋巴细胞计数,血浆HIV-1病毒载量,并在基线及给药后4、8、12、24、36、48周随访肾功能。结果治疗48周后,TDF组的血肌酐(Scr)显著高于对照组(79μmol/L vs.69.7μmol/L,P<0.001),肌酐清除率(Ccr)显著低于对照组(84.1mL/min vs.93.2mL/min,P=0.012)。与基线相比,48周时TDF组Ccr的下降较对照组更显著(-6.7mL/min vs.4.6mL/min,P=0.002),且Ccr在用药最初的4周下降最为明显。结论含TDF与LPV/r方案的HAART,可导致HIV/AIDS病人Ccr下降,应对接受该方案治疗的HIV/AIDS病人进行肾功能监测。

Objective To evaluate the influence of tenofovir disoproxil fumarate （TDF） plus lopinavir/ritonavir （LPV/r）-based on highly active antiretroviral therapy （HAART） regimens on renal function in human immunodefi- ciency virus-1 （HIV-1） infected patients. Methods 75 HIV-1 infected patients with first-line highly active antiret- roviral therapy （HAART） failure were enrolled in TDF group from 13 research centers in China. 75 HIV-1 infected patients exactly matched for gender, age and renal function constituted the control group. In TDF group, patients were treated with TDF＋ LPV/r（lopinavir/ritonavir）＋ 3TC （lamivudine） ; in control group： patients were treated with AZT（zidovudine）/D4T （stavudine） ＋ NVP（nevirapine） ＋ 3TC. All subjects underwent follow-up visits over 48 weeks. CD4 cell count and plasma HIV-1 viral load were assessed at baseline and week 48. The renal function was monitored at each follow-up point. The change in Ccr from baseline to week 48 was compared between two groups. Results Compared with control group, TDF group had a higher level of serum creatinine （79 vs. 69.7 btmol/L, P d0. 001） and a lower ratio of Ccr （84.1 vs. 93.2 mL/min, P=0. 012） at the end of week 48. Patients treated with TDF-based HAART regimens had a greater decline in Ccr than did the control group （--6.7 vs. 4.6mL/min, P= 0. 002） and experienced a significant decline in Ccr during the first 4 weeks of therapy. Conclusions TDF＋ LPV/r- based HAART regimens were associated with a greater decline in renal function over 48 weeks. The renal function should be monitored over the first 4 weeks of therapy especially when TDF＋ LPV/r are used.