对 CD4 细胞计数为 300 至 549×10⁶/L 的 HIV 感染患者给予 HIV-1 免疫原（一种免疫调节剂）的评估：一项随机对照试验。

Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549 x 10(6)/L CD4 cell counts: A randomized controlled trial.

作者信息

Kahn J O, Cherng D W, Mayer K, Murray H, Lagakos S

机构信息

San Francisco General Hospital, 995 Potrero Ave, San Francisco, CA 94110, USA.

出版信息

JAMA. 2000 Nov 1;284(17):2193-202. doi: 10.1001/jama.284.17.2193.

DOI:10.1001/jama.284.17.2193

PMID:11056590

Abstract

CONTEXT

Despite enormous improvements achieved through the use of antiretroviral therapies (ARTs), the risk for eventual human immunodeficiency virus (HIV) disease progression remains high. Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression.

OBJECTIVE

To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs.

DESIGN AND SETTING

Multicenter, double-blind, placebo-controlled, randomized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV.

PATIENTS

Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART (or no therapy) were screened and 2527 were randomized.

INTERVENTIONS

Ten units of HIV-1 Immunogen, derived from a Zairian HIV isolate, inactivated and formulated with incomplete Freund adjuvant, was administered intramuscularly every 12 weeks. The placebo was incomplete Freund adjuvant. Changes in ARTs were allowed.

MAIN OUTCOME MEASURES

HIV progression-free survival; secondary end points included overall survival, changes in HIV RNA, CD4 cell counts, CD4 percentage, body weight, and immunogenicity.

RESULTS

The overall event rate was 1.8 per 100 person-years of follow-up. Fifty-three subjects developed clinical progression in each treatment group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.66-1.42; P =.89). There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups, respectively (RR, 0.81; 95% CI, 0.44-1. 48; P =.49). There were no statistically significant differences between the groups with respect to changes in HIV RNA (P =.59), CD4 percentage (P =.63), or body weight (P =.89). Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group (P =.02).

CONCLUSION

HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival. JAMA. 2000;284:2193-2202.

摘要

背景

尽管通过使用抗逆转录病毒疗法（ARTs）取得了巨大进步，但人类免疫缺陷病毒（HIV）疾病最终进展的风险仍然很高。增强病毒识别免疫机制的药物可能会降低疾病进展。

目的

确定添加HIV-1免疫原是否会比ARTs单独使用时具有更高的临床疗效。

设计与地点

1996年3月开始至1999年5月结束的多中心、双盲、安慰剂对照、随机试验，在美国77个为HIV感染者提供初级护理或转诊护理的中心进行。

患者

筛选出基线CD4细胞计数在300×10⁶/L至549×10⁶/L之间、未患有先前获得性免疫缺陷综合征定义疾病且接受稳定ART（或未接受治疗）的成年HIV感染者，2527人被随机分组。

干预措施

每12周肌肉注射10单位源自扎伊尔HIV毒株的HIV-1免疫原，该免疫原已灭活并与不完全弗氏佐剂配制。安慰剂为不完全弗氏佐剂。允许改变ARTs方案。

主要结局指标

HIV无进展生存期；次要终点包括总生存期、HIV RNA、CD4细胞计数、CD4百分比、体重的变化以及免疫原性。

结果

总事件发生率为每100人年随访1.8例。每个治疗组中有53名受试者出现临床进展（相对风险[RR]，0.97；95%置信区间[CI]，0.66 - 1.42；P = 0.89）。安慰剂组和HIV-1免疫原组分别有19例和23例死亡（RR，0.81；95% CI，0.44 - 1.48；P = 0.49）。两组在HIV RNA变化（P = 0.59）、CD4百分比（P = 0.63）或体重（P = 0.89）方面无统计学显著差异。HIV-1免疫原组受试者的平均CD4细胞计数比安慰剂组增加约10×10⁶/L（P = 0.02）。