Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) Monoclonal Antibody VRC01LS in HIV-1-Exposed Newborn Infants.
J Infect Dis
; 224(11): 1916-1924, 2021 12 01.
Article
em En
| MEDLINE
| ID: mdl-34009371
ABSTRACT
BACKGROUND:
Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs).METHODS:
An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1-exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort.RESULTS:
Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1.CONCLUSIONS:
VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Anti-HIV
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Infecções por HIV
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HIV-1
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Transmissão Vertical de Doenças Infecciosas
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Antirretrovirais
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Anticorpos Amplamente Neutralizantes
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Anticorpos Monoclonais
Limite:
Female
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Humans
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Male
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Newborn
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos