van Leth Frank, Phanuphak Prahpan, Stroes Erik, Gazzard Brian, Cahn Pedro, Raffi François, Wood Robin, Bloch Mark, Katlama Christine, Kastelein John J P, Schechter Mauro, Murphy Robert L, Horban Andrzej, Hall David B, Lange Joep M A, Reiss Peter
International Antiviral Therapy Evaluation Center, Division of Infectious Diseases, Tropical Medicine, and AIDS, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
PLoS Med. 2004 Oct;1(1):e19. doi: 10.1371/journal.pmed.0010019. Epub 2004 Oct 19.
Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV).
Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417), or EFV (n = 289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p = 0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (-4.1%) and an increase for patients receiving EFV (+5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p = 0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs.
NVP-containing ART shows larger increases in HDL-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease.
与开始使用大多数含蛋白酶抑制剂的抗逆转录病毒疗法（ART）的患者相比，开始使用含非核苷类逆转录酶抑制剂（NNRTI）的ART的HIV-1感染患者出现动脉粥样硬化性脂质变化的情况可能较少。我们分析了两种最常用的NNRTI，奈韦拉平（NVP）和依非韦伦（EFV）之间的脂质变化是否存在差异。
对参加2NN研究的NVP和EFV治疗组的患者进行了脂质和脂蛋白的前瞻性分析，这些患者在48周的随访期间继续接受分配的治疗。患者被分配接受NVP（n = 417）或EFV（n = 289）联合司他夫定和拉米夫定治疗。主要终点是高密度脂蛋白胆固醇（HDL-c）、总胆固醇（TC）、TC:HDL-c比值、非HDL-c、低密度脂蛋白胆固醇和甘油三酯在48周内的变化百分比。接受NVP的患者HDL-c的增加（42.5%）显著大于接受EFV的患者（33.7%；p = 0.036），而TC的增加较低（分别为26.9%和31.1%；p = 0.073），导致接受NVP的患者TC:HDL-c比值下降（-4.1%），接受EFV的患者上升（+5.9%；p < 0.001）。接受NVP的患者非HDL-c的增加（24.7%）小于接受EFV的患者（33.6%；p = 0.007），甘油三酯的增加（分别为20.1%和49.0%；p < 0.001）以及低密度脂蛋白胆固醇的增加（分别为35.0%和40.0%；p = 0.378）也是如此。在调整HIV-１RNA和CD4+细胞水平的变化后，这些差异仍然存在，甚至有所增加，这表明药物对脂质的影响超过了因抑制HIV-1感染所能解释的范围。HDL-c的增加幅度与使用研究性HDL-c升高药物时观察到的幅度相同。
与含EFV的治疗方案相比，含NVP的ART使HDL-c升高幅度更大，TC:HDL-c比值降低幅度更大。基于这些发现，基于非核苷类逆转录酶抑制剂，特别是含NVP的蛋白酶抑制剂节省方案，可能会降低冠心病风险。
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