Eron J J, Benoit S L, Jemsek J, MacArthur R D, Santana J, Quinn J B, Kuritzkes D R, Fallon M A, Rubin M
University of North Carolina at Chapel Hill 27599-7030, USA.
N Engl J Med. 1995 Dec 21;333(25):1662-9. doi: 10.1056/NEJM199512213332502.
The reverse-transcriptase inhibitor lamivudine has in vitro synergy with zidovudine against the human immunodeficiency virus (HIV). We studied the activity and safety of lamivudine plus zidovudine as compared with either drug alone as treatment for patients with HIV infection, most of whom had not previously received zidovudine.
Three hundred sixty-six patients with 200 to 500 CD4+ cells per cubic millimeter who had received zidovudine for four weeks or less were randomly assigned to treatment with one of four regimens: 300 mg of lamivudine every 12 hours; 200 mg of zidovudine every 8 hours; 150 mg of lamivudine every 12 hours plus zidovudine; or 300 mg of lamivudine every 12 hours plus zidovudine. The study was double-blind and lasted 24 weeks, with an extension phase for another 28 weeks.
Over the 24-week period, the low-dose and high-dose regimens combining lamivudine and zidovudine were associated with greater increases in the CD4+ cell count (P = 0.002 and P = 0.015, respectively) and the percentage of CD4+ cells (P < 0.001 for both) and with greater decreases in plasma levels of HIV-1 RNA (P < 0.001 for both) than was treatment with zidovudine alone. Combination therapy was also more effective than lamivudine alone in lowering plasma HIV-1 RNA levels and increasing the percentage of CD4+ cells (P < 0.001 for all comparisons), and these advantages persisted through 52 weeks. Adverse events were no more frequent with combination therapy than with zidovudine alone.
In HIV-infected patients with little or no prior antiretroviral therapy, treatment with a combination of lamivudine and zidovudine is well tolerated over a one-year period and produces more improvement in immunologic and virologic measures than does treatment with either agent alone.
逆转录酶抑制剂拉米夫定在体外与齐多夫定对人类免疫缺陷病毒（HIV）具有协同作用。我们研究了拉米夫定加齐多夫定与单独使用这两种药物之一相比，作为HIV感染患者治疗方法的活性和安全性，这些患者大多数之前未接受过齐多夫定治疗。
366例每立方毫米有200至500个CD4 +细胞且接受齐多夫定治疗四周或更短时间的患者被随机分配接受四种治疗方案之一：每12小时服用300毫克拉米夫定；每8小时服用200毫克齐多夫定；每12小时服用150毫克拉米夫定加齐多夫定；或每12小时服用300毫克拉米夫定加齐多夫定。该研究为双盲研究，持续24周，并另有28周的延长期。
在24周期间，与单独使用齐多夫定治疗相比，低剂量和高剂量的拉米夫定与齐多夫定联合治疗方案使CD4 +细胞计数增加更多（分别为P = 0.002和P = 0.015）以及CD4 +细胞百分比增加更多（两者均P < 0.001），并且使血浆HIV-1 RNA水平下降更多（两者均P < 0.001）。联合治疗在降低血浆HIV-1 RNA水平和增加CD4 +细胞百分比方面也比单独使用拉米夫定更有效（所有比较均P < 0.001），并且这些优势持续到52周。联合治疗的不良事件发生率并不比单独使用齐多夫定更高。
在几乎未接受过或未接受过抗逆转录病毒治疗的HIV感染患者中，拉米夫定和齐多夫定联合治疗在一年期间耐受性良好，并且在免疫和病毒学指标方面比单独使用任何一种药物治疗有更大改善。
