Kumar P N, Rodriguez-French A, Thompson M A, Tashima K T, Averitt D, Wannamaker P G, Williams V C, Shaefer M S, Pakes G E, Pappa K A
Georgetown University Medical Center, Washington, DC 20007, USA.
HIV Med. 2006 Mar;7(2):85-98. doi: 10.1111/j.1468-1293.2006.00346.x.
To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV.
An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL.
Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions.
The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms.
Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses.
比较三联抗反转录病毒片（阿巴卡韦300毫克/拉米夫定150毫克/齐多夫定300毫克；TZV）每日两次给药方案、双汰芝（拉米夫定150毫克/齐多夫定300毫克复方片剂；COM）+奈非那韦（NFV）以及司他夫定（d4T）+拉米夫定（3TC）+NFV的脂质和代谢效应、疗效及安全性。
一项国际性、4期、开放标签、平行组、34中心研究纳入了254例未患糖尿病、未接受过抗逆转录病毒治疗、HIV感染的门诊患者，其HIV-1 RNA水平>1000 HIV-1 RNA拷贝/毫升且≤200,000拷贝/毫升，CD4细胞计数>50细胞/微升。
患者按1:1:1随机分为每日两次服用TZV组（n = 85）、每日两次服用COM/NFV 1250毫克组（n = 88）或每日两次服用d4T 40毫克+3TC 150毫克+NFV 1250毫克组（n = 81），疗程96周。采用协方差分析（ANCOVA）比较总体人群以及性别和种族亚组中空腹血脂相对于基线的变化。使用比例差异的95%置信区间（CI）比较HIV-1 RNA<50和<400拷贝/毫升的患者比例。
研究人群具有多样性（50%为女性，40%为黑人，37%为西班牙裔）。平均基线低密度脂蛋白（LDL）胆固醇为99毫克/分升，HIV-1 RNA为4.43 log10拷贝/毫升，CD4细胞计数为355细胞/微升。在第96周时，TZV组空腹LDL胆固醇变化极小[相对于基线的最小二乘均值（LSM）变化为-8毫克/分升]，但d4T/3TC/NFV组和COM/NFV组升高（分别为+29和+19毫克/分升；与TZV组相比，P<0.001）。在男性和女性中，TZV组第96周的LDL胆固醇水平显著低于其他两个治疗组，在西班牙裔和黑人患者中低于d4T/3TC/NFV组。在黑人患者中，TZV组第96周LDL胆固醇相对于基线的LSM变化显著小于d4T/3TC/NFV组（+1对+39毫克/分升；P = 0.003）。接受TZV治疗的患者中总胆固醇>200毫克/分升的比例（30%）低于COM/NFV组（50%）或d4T/3TC/NFV组（60%；与TZV组相比，P = 0.005）。高密度脂蛋白（HDL）胆固醇在任何治疗中均无明显变化。尽管甘油三酯升高，但在接受TZV治疗的女性和西班牙裔患者中变化最小。总体人群和亚组中对治疗的病毒学和CD4反应相似。NFV组腹泻报告更常见，ZDV组恶心报告更常见。
在96周内，每日两次服用TZV对LDL胆固醇的影响明显小于每日两次服用COM/NFV或d4T/3TC/NFV，尤其是在女性和黑人患者中，且病毒学和CD4反应相似。
