HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.
HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.
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DOI：
10.1038/nature18929
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发表时间：
2016-07-28
期刊：
影响因子：
64.8
通讯作者：
Caskey, Marina
中科院分区：
文献类型：
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作者：
Scheid, Johannes F.;Horwitz, Joshua A.;Bar-On, Yotam;Kreider, Edward F.;Lu, Ching-Lan;Lorenzi, Julio C. C.;Feldmann, Anna;Braunschweig, Malte;Nogueira, Lilian;Oliveira, Thiago;Shimeliovich, Irina;Patel, Roshni;Burke, Leah;Cohen, Yehuda Z.;Hadrigan, Sonya;Settler, Allison;Witmer-Pack, Maggi;West, Anthony P., Jr.;Juelg, Boris;Keler, Tibor;Hawthorne, Thomas;Zingman, Barry;Gulick, Roy M.;Pfeifer, Nico;Learn, Gerald H.;Seaman, Michael S.;Bjorkman, Pamela J.;Klein, Florian;Schlesinger, Sarah J.;Walker, Bruce D.;Hahn, Beatrice H.;Nussenzweig, Michel C.;Caskey, Marina
HIV-1感染者联合抗逆转录病毒治疗的中断会导致病毒快速反弹。在此，我们报告了一项 IIa 期开放标签临床试验的结果，该试验在 13 名 HIV-1 感染者的分析治疗中断的情况下评估了 3BNC117，这是一种针对 HIV-1 Env 的 CD4 结合位点的广泛且有效的中和抗体 (bNAb)。招募了具有 3BNC117 敏感病毒生长培养物的参与者。两次或四次 30 mg kg−1 3BNC117 输注，分别间隔 3 或 2 周，通常耐受性良好。输注与两次输注后病毒反弹延迟 5-9 周相关，四次输注后病毒反弹延迟长达 19 周，即平均分别为 6.7 周和 9.9 周，而历史对照为 2.6 周（P < 0.00001）。反弹病毒主要由单一原病毒产生。在大多数个体中，新出现的病毒表现出更强的抵抗力，表明病毒正在逃脱。然而，30% 的参与者仍然受到抑制，直到抗体浓度降至 20 μg ml−1 以下，并且除其中一人外，所有个体中出现的病毒均未表现出对 3BCN117 的明显抵抗力，表明在 9-19 周的时间内未能逃脱。我们得出的结论是，在人类分析治疗中断期间，给予 3BNC117 对潜伏病毒库中出现的 HIV-1 产生强大的选择性压力。
Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env, in the setting of analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg kg−1 infusions of 3BNC117, separated by 3 or 2 weeks, respectively, are generally well tolerated. Infusions are associated with a delay in viral rebound for 5–9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals, emerging viruses show increased resistance, indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml−1, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9–19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.
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DOI：
10.1126/science.aaf1279
发表时间：
2016-05-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lu CL;Murakowski DK;Bournazos S;Schoofs T;Sarkar D;Halper-Stromberg A;Horwitz JA;Nogueira L;Golijanin J;Gazumyan A;Ravetch JV;Caskey M;Chakraborty AK;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Caskey M;Klein F;Lorenzi JC;Seaman MS;West AP Jr;Buckley N;Kremer G;Nogueira L;Braunschweig M;Scheid JF;Horwitz JA;Shimeliovich I;Ben-Avraham S;Witmer-Pack M;Platten M;Lehmann C;Burke LA;Hawthorne T;Gorelick RJ;Walker BD;Keler T;Gulick RM;Fätkenheuer G;Schlesinger SJ;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
5.4
作者：
Lynch, Rebecca M.;Wong, Patrick;Mascola, John R.
通讯作者：
Mascola, John R.
影响因子：
64.5
作者：
Ho YC;Shan L;Hosmane NN;Wang J;Laskey SB;Rosenbloom DI;Lai J;Blankson JN;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF