Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.
Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.
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DOI：
10.1056/nejmoa1310566
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发表时间：
2013-11-28
期刊：
影响因子：
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通讯作者：
HVTN 505 Study Team
中科院分区：
文献类型：
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作者：
Hammer SM;Sobieszczyk ME;Janes H;Karuna ST;Mulligan MJ;Grove D;Koblin BA;Buchbinder SP;Keefer MC;Tomaras GD;Frahm N;Hural J;Anude C;Graham BS;Enama ME;Adams E;DeJesus E;Novak RM;Frank I;Bentley C;Ramirez S;Fu R;Koup RA;Mascola JR;Nabel GJ;Montefiori DC;Kublin J;McElrath MJ;Corey L;Gilbert PB;HVTN 505 Study Team
一种安全有效的预防人类免疫缺陷病毒1型（HIV-1）感染的疫苗是全球的优先事项。我们测试了DNA引物重组腺病毒5型增强（DNA/rAd5）疫苗方案在美国HIV-1感染风险增加的人群中的有效性。在21个地点，我们随机分配2504名男性或与男性发生性关系的变性女性接受DNA/rAd5疫苗（1253名参与者）或安慰剂（1251名参与者）。我们评估了从第28周到第24个月的HIV-1感染（称为第28周+感染）、病毒载量设定点（诊断后10至20周的平均血浆HIV-1 RNA水平）和安全性。在第0、4和8周接种6质粒DNA疫苗（表达进化支B Gag、Pol以及来自进化支A、B和C的Nef和Env蛋白）。在第24周给予rAd5载体增强（表达进化支B Gag-Pol融合蛋白和来自进化支A、B和C的Env糖蛋白）。2013年4月，数据和安全监测委员会建议停止疫苗接种，理由是缺乏效力。初步分析显示，28周后，疫苗组有27名参与者被诊断出感染，安慰剂组有21名参与者被诊断出感染（疫苗有效性为- 25.0%；95%可信区间为- 121.2至29.3;P = 0.44），平均病毒载量设定点分别为4.46和4.47 HIV-1 RNA log10拷贝/毫升。对研究期间所有感染的分析（疫苗组41例，安慰剂组31例）也显示疫苗缺乏疗效（P = 0.28）。疫苗方案的副作用是可以接受的。在研究人群中，DNA/rAd5疫苗方案既没有降低HIV-1获得率，也没有降低病毒载量设定点。（由国家过敏和传染病研究所资助；ClinicalTrials.gov号码，NCT00865566。）
A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime–recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States. At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24. In April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, −25.0%; 95% confidence interval, −121.2 to 29.3; P = 0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P = 0.28). The vaccine regimen had an acceptable side-effect profile. The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.)