O'Brien W A, Hartigan P M, Martin D, Esinhart J, Hill A, Benoit S, Rubin M, Simberkoff M S, Hamilton J D
Department of Medicine, West Los Angeles Veterans Affairs Medical Center, CA 90073, USA.
N Engl J Med. 1996 Feb 15;334(7):426-31. doi: 10.1056/NEJM199602153340703.
Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression.
We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma.
Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent).
Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well.
抗逆转录病毒药物的临床试验可能需要数年才能完成，因为所测量的结果是进展为获得性免疫缺陷综合征（艾滋病）或死亡。使用诸如CD4 +淋巴细胞计数、1型人类免疫缺陷病毒（HIV - 1）RNA和β2 -微球蛋白血浆水平的变化等终点指标可以加速试验，但这些替代指标是否是疾病进展的有效预测指标尚不确定。
我们分析了退伍军人事务部艾滋病合作研究的数据，该研究比较了齐多夫定立即治疗与延迟治疗的效果。在储存的血浆中测量患者的HIV - 1 RNA和β2 -微球蛋白血浆水平。
在立即治疗组的129例患者中，34例病情进展为艾滋病，而延迟治疗组的141例患者中有57例（P = 0.03）。进展为艾滋病与基线CD4 +淋巴细胞计数（P = 0.001）和HIV - 1 RNA血浆水平（P < 0.001）密切相关，但与β2 -微球蛋白基线水平无关（P = 0.14）。在齐多夫定治疗的前六个月中，HIV - 1 RNA血浆水平至少降低75%占治疗益处的59%，治疗益处定义为无进展至艾滋病（95%置信区间，13%至112%）。血浆β2 -微球蛋白水平和CD4 +淋巴细胞计数对治疗效果的解释较少。血浆HIV - 1 RNA水平降低75%加上CD4 +淋巴细胞计数增加10%可以解释79%的治疗效果（95%置信区间，27%至145%）。
治疗引起的血浆HIV - 1 RNA水平和CD4 +淋巴细胞计数的变化共同是HIV相关疾病临床进展的有效预测指标，可用于评估齐多夫定以及可能其他抗逆转录病毒药物的疗效。
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