Autran Brigitte, Murphy Robert L, Costagliola Dominique, Tubiana Roland, Clotet Bonaventura, Gatell Jose, Staszewski Schlomo, Wincker Norma, Assoumou Lambert, El-Habib Raphaelle, Calvez Vincent, Walker Bruce, Katlama Christine
UPMC Univ Paris 06, UMR_543, France.
AIDS. 2008 Jul 11;22(11):1313-22. doi: 10.1097/QAD.0b013e3282fdce94.
Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients.
Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/microl, CD4 nadir less than 400 cells/microl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo. The primary endpoint was vaccine immunogenicity at week 24 measured by enzyme-linked immunospot-interferon-gamma against the HIV-gag-reverse transcriptase-nef vaccine sequences. Secondary endpoints included time to treatment resumption and viral quantitation following treatment interruption at week 24. Criteria to resume therapy included CD4 T-cell count decline less than 250 cells/microl or 50% decrease from baseline or pHIV-RNA more than 50,000 copies/ml.
Sixty-five patients enrolled. Changes from baseline in HIV-specific T cells in the four injection arms (+480 spot-forming cells/M-peripheral blood mononuclear cell) were significant compared to placebo (+8; P = 0.014), but not in the three injection arms (+322). The week 36 pHIV-RNA (log10 copies/ml) after treatment interruption was higher in the four (4.71; P = 0.023) and three (4.82; P = 0.009) injection arms compared to placebo (4.40). Percentages of patients reaching treatment resumption criteria by week 48 were 74, 55 and 23% in the three respective arms (P = 0.013). Two independent factors influenced time to therapy resumption: immunization (hazards ratio = 2.7, P = 0.048 for three injections; hazards ratio = 4.1, P = 0.003 for four injections) and CD4 nadir (hazards ratio = 0.4, P = 0.002).
Significant immunogenicity was induced by vCP1452; however, this strategy was independently associated with a shorter time to resume therapy and higher viral rebound.
评估两种使用ALVAC-HIV重组金丝雀痘疫苗（vCP1452）的免疫策略在接受治疗的HIV感染患者中的免疫原性和临床疗效。
一项针对CD4 T细胞计数超过350个细胞/微升、CD4最低点低于400个细胞/微升且pHIV-RNA低于400拷贝/毫升的慢性HIV感染患者进行vCP1452免疫接种的随机、双盲、安慰剂对照的II期研究。患者被随机分为三组，分别在第0、4、8、20周接受四次注射；在第4、8、20周接受三次注射；以及接受安慰剂注射。主要终点是在第24周时通过酶联免疫斑点法检测针对HIV- gag -逆转录酶- nef疫苗序列的干扰素-γ来评估疫苗免疫原性。次要终点包括恢复治疗的时间以及在第24周治疗中断后的病毒定量。恢复治疗的标准包括CD4 T细胞计数下降少于250个细胞/微升或比基线下降50%或pHIV-RNA超过50,000拷贝/毫升。
65名患者入组。与安慰剂组（增加8个斑点形成细胞/百万外周血单个核细胞）相比，四次注射组（增加480个斑点形成细胞/百万外周血单个核细胞）HIV特异性T细胞相对于基线的变化具有显著差异（P = 0.014），但三次注射组（增加322个斑点形成细胞/百万外周血单个核细胞）无显著差异。与安慰剂组（4.40）相比，四次注射组（4.71；P = 0.023）和三次注射组（4.82；P = 0.009）在治疗中断后第36周的pHIV-RNA（log10拷贝/毫升）更高。在第48周达到恢复治疗标准的患者百分比在三个组中分别为74%、55%和23%（P = 0.013）。有两个独立因素影响恢复治疗的时间：免疫接种（三次注射的风险比 = 2.7，P = 0.048；四次注射的风险比 = 4.1，P = 0.003）和CD4最低点（风险比 = 0.4，P = 0.002）。
vCP1452诱导了显著的免疫原性；然而，这种策略与恢复治疗的时间较短和病毒反弹较高独立相关。
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