Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants
| Autor: | Megan Valentine, Robert T. Bailer, Jeffrey T. Safrit, John R. Mascola, Lisa-Gaye E. Robinson, Gerhard Theron, Charlotte Perlowski, Andrew Wiznia, Impaact P s Protocol Team, Barney S. Graham, R Leavitt Morrison, Bonnie J. Mathieson, Lynette Purdue, Rohan Hazra, Betsy Smith, Elizabeth J. McFarland, Edmund V. Capparelli, Tapiwa Mbengeranwa, Paul Harding, Bob C. Lin, Lynne M. Mofenson, Petronella Muresan, Coleen K. Cunningham |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Pediatric AIDS Erythema Infectious Disease Transmission Human immunodeficiency virus (HIV) Breastfeeding Physiology HIV Infections Reproductive health and childbirth HIV Antibodies medicine.disease_cause Medical and Health Sciences 0302 clinical medicine Monoclonal Immunology and Allergy Vertical 030212 general & internal medicine Hiv transmission Pediatric biology Transmission (medicine) Subcutaneous Antibodies Monoclonal Biological Sciences IMPAACT P1112 team Infectious Diseases 6.1 Pharmaceuticals HIV/AIDS Female Antibody medicine.symptom Infection Injections Subcutaneous Clinical Trials and Supportive Activities Breast milk Microbiology Antibodies Injections VRC01 Vaccine Related 03 medical and health sciences Pharmacokinetics Clinical Research medicine Humans mother-to-child transmission of HIV business.industry broadly neutralizing antibodies Prevention Infant Newborn Infant Evaluation of treatments and therapeutic interventions Perinatal Period - Conditions Originating in Perinatal Period Newborn neonates Infectious Disease Transmission Vertical United States 030104 developmental biology Good Health and Well Being Africa biology.protein HIV-1 Linear Models Immunization business Broadly Neutralizing Antibodies |
| Zdroj: | The Journal of infectious diseases, vol 222, iss 4 |
| Popis: | BackgroundAlthough mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission.MethodsA Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis.ResultsForty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1–6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding.ConclusionsSubcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants. |
| Databáze: | OpenAIRE |
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