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
| Autor: | Gerhard Theron, Mobeen H. Rathore, Edmund V. Capparelli, Charlotte Perlowski, John R. Mascola, Allison L. Agwu, Lynette Purdue, Elizabeth J. McFarland, Adrian B. McDermott, Rohan Hazra, Coleen K. Cunningham, Alison Taylor, Paul Harding, Barney S. Graham, Patricia Morgan, Betsy Smith, Hilda Mujuru, Murli Purswani, Britta Flach, Bob C. Lin, Impaact P s Protocol Team, Petronella Muresan |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.drug_class Human immunodeficiency virus (HIV) HIV Infections HIV Antibodies Monoclonal antibody medicine.disease_cause Major Articles and Brief Reports Pharmacokinetics Humans Immunology and Allergy Medicine Dose-Response Relationship Drug business.industry Transmission (medicine) Infant Newborn Antibodies Monoclonal Safety tolerability Infectious Disease Transmission Vertical Hiv 1 prevention Infectious Diseases Long acting Anti-Retroviral Agents Immunology Cohort HIV-1 Female business Broadly Neutralizing Antibodies Half-Life |
| Zdroj: | J Infect Dis |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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