Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.
Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.
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DOI：
10.1056/nejmoa2031738
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发表时间：
2021-03-18
期刊：
影响因子：
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通讯作者：
HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams
中科院分区：
文献类型：
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作者：
Corey L;Gilbert PB;Juraska M;Montefiori DC;Morris L;Karuna ST;Edupuganti S;Mgodi NM;deCamp AC;Rudnicki E;Huang Y;Gonzales P;Cabello R;Orrell C;Lama JR;Laher F;Lazarus EM;Sanchez J;Frank I;Hinojosa J;Sobieszczyk ME;Marshall KE;Mukwekwerere PG;Makhema J;Baden LR;Mullins JI;Williamson C;Hural J;McElrath MJ;Bentley C;Takuva S;Gomez Lorenzo MM;Burns DN;Espy N;Randhawa AK;Kochar N;Piwowar-Manning E;Donnell DJ;Sista N;Andrew P;Kublin JG;Gray G;Ledgerwood JE;Mascola JR;Cohen MS;HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams
广泛中和抗体（bnAb）是否可用于预防人类免疫缺陷病毒1型（HIV-1）感染尚不清楚。我们在HVTN 704/HPTN 085试验中招募了美洲和欧洲的高风险顺性别男性和跨性别者，在HVTN 703/HPTN 081试验中招募了撒哈拉以南非洲的高风险女性。参与者被随机分配每8周接受一次bnAb（VRC 01）输注，剂量为10或30 mg/kg（分别为低剂量组和高剂量组）或安慰剂，共输注10次。每4周进行一次HIV-1检测。用TZM-bl测定法测量获得的分离株的VRC 01 80%抑制浓度（IC 80）。在每项试验中，治疗组之间不良事件的数量和严重程度相似。在HVTN 704/HPTN 085的2699名参与者中，低剂量组有32人感染HIV-1，高剂量组有28人感染，安慰剂组有38人感染。在HVTN 703/HPTN 081的1924名受试者中，低剂量组有28人感染，高剂量组有19人感染，安慰剂组有29人感染。在HVTN 704/HPTN 085中，合并的VRC 01组中每100人-年的HIV-1感染发生率为2.35，安慰剂组为2.98（估计预防效果，26.6%; 95%置信区间[CI]，-11.7至51.8; P = 0.15），HVTN 703/HPTN 081中每100人-年的发生率在合并的VRC 01组中为2.49，在安慰剂组中为3.10（估计的预防疗效为8.8%; 95% CI为-45.1至42.6; P = 0.70）。在预先设定的分析中，将试验数据汇总，每100人-年中VRC 01敏感分离株（IC 80 <1 μg/ml）感染的发生率在VRC 01接受者中为0.20，在安慰剂接受者中为0.86（估计的预防疗效为75.4%; 95%CI为45.5至88.9）。各VRC 01剂量和试验对敏感分离株的预防效果相似; VRC 01未阻止其他HIV-1分离株的获得。VRC 01并没有比安慰剂更有效地预防总体HIV-1感染，但对VRC 01敏感的HIV-1分离株的分析提供了bnAb预防有效的概念验证。（由国家过敏和传染病研究所支持; HVTN 704/HPTN 085和HVTN 703/HPTN 081 ClinicalTrials.gov编号，NCT 02716675和NCT 02568215。
Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay. Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], −11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, −45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates. VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.)