Chêne G, Binquet C, Moreau J F, Neau D, Pellegrin I, Malvy D, Ceccaldi J, Lacoste D, Dabis F
Unité INSERM 330, Université Victor Segalen Bordeaux 2, France.
AIDS. 1998 Dec 3;12(17):2313-20. doi: 10.1097/00002030-199817000-00013.
To study the relationship between the CD4+ cell response after initiation of protease inhibitors and the occurrence of opportunistic infections and survival.
Prospective observational cohort study.
HIV-1-seropositive subjects followed-up in HIV centres of Bordeaux University Hospital, Southwest France who were prescribed at least one available protease inhibitor between January and December 1996 were included in this analysis. A Cox model estimated the independent effect of baseline covariates and CD4+ cell response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining opportunistic infection, new AIDS-defining events, new AIDS-defining opportunistic infection or death.
A total of 556 HIV-positive patients were prescribed at least one protease inhibitor: 34% saquinavir, 52% indinavir, and 14% ritonavir. Median CD4+ cell count at baseline was 95 x 10(6)/l and mean plasma HIV RNA was 5.0 log10 copies/ml. After a median follow-up of 230 days, 65 patients experienced a new episode of opportunistic infection, 79 patients experienced at least one AIDS-defining event, and 24 had died. On average, the increase in CD4+ cell count was 42 x 10(6)/l (SD, 74) after a median of 49 days. In the multivariate analysis of opportunistic infection or death, each 50% higher CD4+ cell count at baseline was associated with a 23% reduction [95% confidence interval (CI), 14-30] of risk. Each 50% increase in CD4+ cell count during follow-up was associated with a 9% reduction (95% CI, 2-15) of risk, adjusted for the presence of AIDS prior to protease inhibitor therapy (hazard ratio, 3.76 versus absence of AIDS; P < 0.01) and haemoglobin level (hazard ratio, 0.48 if > 11 g/dl versus <11 g/dl; P < 0.01).
Our results show, at least indirectly, how protease inhibitors might produce clinical stabilization. This result may be due to improved functionality of CD4+ cells in patients started on protease inhibitors.
研究开始使用蛋白酶抑制剂后CD4+细胞反应与机会性感染的发生及生存之间的关系。
前瞻性观察队列研究。
纳入1996年1月至12月在法国西南部波尔多大学医院的艾滋病中心接受随访、至少使用过一种可用蛋白酶抑制剂的HIV-1血清阳性受试者。采用Cox模型估计基线协变量和作为时间依赖性协变量的CD4+细胞反应对新的艾滋病定义的机会性感染、新的艾滋病定义事件、新的艾滋病定义的机会性感染或死亡发生的独立影响。
共有556名HIV阳性患者至少使用过一种蛋白酶抑制剂：34%使用沙奎那韦，52%使用茚地那韦，14%使用利托那韦。基线时CD4+细胞计数中位数为95×10⁶/l，血浆HIV RNA平均水平为5.0 log₁₀拷贝/ml。中位随访230天后，65例患者经历了新的机会性感染发作，79例患者经历了至少一次艾滋病定义事件，24例患者死亡。平均而言，在中位49天后，CD4+细胞计数增加了42×10⁶/l（标准差，74）。在机会性感染或死亡的多变量分析中，基线时CD4+细胞计数每高出50%，风险降低23%[95%置信区间（CI），14-30]。随访期间CD4+细胞计数每增加50%，风险降低9%（95%CI，2-15），对蛋白酶抑制剂治疗前是否存在艾滋病（风险比，存在艾滋病为3.76，无艾滋病为1；P<0.01）和血红蛋白水平（风险比，血红蛋白>11 g/dl为0.48，<11 g/dl为1；P<0.01）进行了校正。
我们的结果至少间接显示了蛋白酶抑制剂可能如何实现临床稳定。这一结果可能是由于开始使用蛋白酶抑制剂的患者中CD4+细胞功能得到改善。
