Riddler Sharon A, Zheng Lu, Durand Christine M, Ritz Justin, Koup Richard A, Ledgerwood Julie, Bailer Robert T, Koletar Susan L, Eron Joseph J, Keefer Michael C, Macatangay Bernard J C, Cyktor Joshua C, Mellors John W
University of Pittsburgh, Pittsburgh, Pennsylvania.
Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, Massachusetts.
Open Forum Infect Dis. 2018 Oct 20;5(10):ofy242. doi: 10.1093/ofid/ofy242. eCollection 2018 Oct.
Broadly neutralizing monoclonal antibodies (bnMAbs) may promote clearance of HIV-1-expressing cells through antibody-dependent cell-mediated cytotoxicity. We evaluated the effect of the CD4-binding site bnMAb, VRC01, on measures of HIV-1 persistence in chronically infected individuals.
A5342 was a phase 1, randomized, double-blind, placebo-controlled, parallel-arm study. Participants on effective antiretroviral therapy (ART) were randomized to receive 2 infusions of VRC01 (40 mg/kg) at entry and week 3, and 2 infusions of placebo (saline) at weeks 6 and 9; or 2 infusions of placebo at entry and week 3, and 2 infusions of VRC01 at weeks 6 and 9.
Infusion of VRC01 was safe and well tolerated. The median fold-change in the cell-associated HIV-1 RNA/DNA ratio from baseline to week 6 was 1.12 and 0.83 for the VRC01 and placebo arms, respectively, with no significant difference between arms ( = .16). There were no significant differences in the proportions with residual plasma viremia ≥1 copies/mL or in phorbol 12-myristate 13-acetate/ionomycin-induced virus production from CD4 T cells between arms (both > .05).
In individuals with chronic HIV-1 infection on ART, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV-1 RNA/DNA levels, or stimulated virus production from CD4 T cells.
NCT02411539.
广泛中和单克隆抗体（bnMAbs）可能通过抗体依赖性细胞介导的细胞毒性促进HIV-1表达细胞的清除。我们评估了CD4结合位点bnMAb VRC01对慢性感染个体中HIV-1持续存在指标的影响。
A5342是一项1期随机双盲安慰剂对照平行组研究。接受有效抗逆转录病毒治疗（ART）的参与者被随机分为两组，一组在入组时和第3周接受2次VRC01（40mg/kg）输注，在第6周和第9周接受2次安慰剂（生理盐水）输注；另一组在入组时和第3周接受2次安慰剂输注，在第6周和第9周接受2次VRC01输注。
VRC01输注安全且耐受性良好。从基线到第6周，VRC01组和安慰剂组细胞相关HIV-1 RNA/DNA比值的中位数变化倍数分别为1.12和0.83，两组之间无显著差异（P = 0.16）。两组之间血浆病毒血症残留≥1拷贝/mL的比例或佛波酯12-肉豆蔻酸酯13-乙酸盐/离子霉素诱导的CD4 T细胞病毒产生比例均无显著差异（均P>0.05）。
在接受ART的慢性HIV-1感染个体中，VRC01输注安全且耐受性良好，但不影响血浆病毒血症、细胞内HIV-1 RNA/DNA水平或CD4 T细胞刺激产生的病毒。
NCT02411539。
