Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07–523LS in Newborn Infants Exposed to HIV-1
Rattachement africain : us, Afrique du Sud, Zimbabwe. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by the use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07-523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07-523LS. METHODS: VRC07-523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (cohort 1; N = 11, enrolled in USA) and breastfed (cohort 2; N = 11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1. Breastfed infants (cohort 2) received a second 100-mg dose at 12 weeks if still receiving breastmilk. All infants received antiretroviral prophylaxis in addition to VRC07-523LS. VRC07-523LS levels were compared to VRC01 levels, as determined previously in this study. RESULTS: Local reactions (all grade ≤ 2) occurred after dose 1 in 18% of infants in cohort 1 and after doses 1 and 2 in 100% of infants in cohort 2. The VRC07-523LS dose at birth (mean 26 mg/kg) achieved a mean ± SD plasma level of 222.3 ± 71.6 mcg/mL by 24 hours and 18.4 ± 7.2 mcg/mL at week 12, prior to dose 2. The pre-established target of ≥ 10 mcg/mL at week 12 was met in 94% of infants. The terminal half-life of VRC07-523LS was observed to be 39.2 ± 5.0 days. At week 4 and week 8, bNAb levels were significantly higher (P ≤ .002) after one dose of VRC07-523LS, compared to one dose of VRC01 (20 mg/kg). No infant included in the study acquired HIV-1. CONCLUSIONS: VRC07-523LS was well tolerated with pharmacokinetics that support further studies of potent long-acting bNAbs together with antiretrovirals to prevent HIV-1 acquisition in infants.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07–523LS in Newborn Infants Exposed to HIV-1
- Date Crossref
- 16/01/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Children's Hospital of Orange County Division of Infectious Diseases pays non établi dans la noticeÉtablissement de santé
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University of California Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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University of Colorado Anschutz Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Frontier Science & Technology Research Foundation pays non établi dans la noticeOrganisation à but non lucratif
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University of California San Diego pays non établi dans la noticeUniversité ou école supérieure
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University of Montana pays non établi dans la noticeUniversité ou école supérieure
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Family Health International 360 pays non établi dans la noticeOrganisation à but non lucratif
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National Institute of Allergy and Infectious Diseases Division of AIDS pays non établi dans la noticeStructure de recherche
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National Institutes of Health pays non établi dans la noticeOrganisme public
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Eunice Kennedy Shriver National Institute of Child Health and Human Development pays non établi dans la noticeStructure de recherche
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Kelly Services (United States) pays non établi dans la noticeEntreprise
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Stellenbosch University Stellenbosch University, Afrique du Sud (code pays fourni par la source)Université ou école supérieure
Division of Infectious Diseases — Children's Hospital of Orange County, Department of Pediatrics — University of California et Department of Pediatrics — University of Colorado Anschutz, avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud, Zimbabwe.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.