Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials

被引：17

作者：

Huang, Yunda ^{[1
,2
,3
]}

Naidoo, Logashvari ^{[4
]}

Zhang, Lily ^{[1
]}

Carpp, Lindsay N. ^{[1
]}

Rudnicki, Erika ^{[1
]}

Randhawa, April ^{[1
]}

Gonzales, Pedro ^{[5
]}

McDermott, Adrian ^{[6
]}

Ledgerwood, Julie ^{[6
]}

Lorenzo, Margarita M. Gomez ^{[7
]}

Burns, David ^{[7
]}

DeCamp, Allan ^{[1
,2
]}

Juraska, Michal ^{[1
,2
]}

Mascola, John ^{[6
]}

Edupuganti, Srilatha ^{[8
]}

Mgodi, Nyaradzo ^{[9
]}

Cohen, Myron ^{[10
,11
]}

Corey, Lawrence ^{[12
,13
]}

Andrew, Philip ^{[14
]}

Karuna, Shelly ^{[1
]}

Gilbert, Peter B. ^{[1
,2
,15
]}

Mngadi, Kathryn ^{[16
]}

Lazarus, Erica ^{[17
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[2] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[3] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

[4] South African Med Res Council, HIV Prevent Res Unit, Durban, South Africa

[5] Asociac Civil Impacta Salud & Educ, Lima, Peru

[6] NIAID, Vaccine Res Ctr VRC, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[7] NIAID, Div Aids, Bethesda, MD 20892 USA

[8] Emory Univ, Div Infect Dis, Dept Med, Decatur, GA USA

[9] Univ Zimbabwe, Clin Trials Res Ctr, Coll Hlth Sci, Harare, Zimbabwe

[10] Univ N Carolina, Sch Med, Div Infect Dis, Dept Med, Chapel Hill, NC 27599 USA

[11] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC 27515 USA

[12] Univ Washington, Dept Med, Seattle, WA USA

[13] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA

[14] Family Hlth Int, Durham, NC USA

[15] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[16] Ctr AIDS Programme Res South Africa, Durban, South Africa

[17] Univ Witwatersrand, Perinatal HIV Res Unit PHRU, Fac Hlth Sci, Johannesburg, Gauteng, South Africa

来源：

EBIOMEDICINE | 2021年 / 64卷

关键词：

Antibody mediated prevention trials; Population pharmacokinetics; VRC01; Broadly neutralising antibodies; HIV-1; MONOCLONAL-ANTIBODY; PROTECTION; DIVERSITY; SAFETY;

D O I：

10.1016/j.ebiom.2020.103203

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The phase 2b AMP trials are testing whether the broadly neutralising antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modelling of longitudinal serum VRC01 concentrations to characterise pharmacokinetics and predict HIV-1 neutralisation coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralisation coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralisation coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralisation correlate with HIV incidence. (C) 2020 The Authors. Published by Elsevier B.V.

引用

页数：11

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