Elizabeth J McFarland1, Coleen K Cunningham2, Petronella Muresan3, Edmund V Capparelli4, Charlotte Perlowski5, Patricia Morgan5, Betsy Smith6, Rohan Hazra7, Lynette Purdue8, Paul A Harding1, Gerhard Theron9, Hilda Mujuru10, Allison Agwu11, Murli Purswani12, Mobeen H Rathore13, Britta Flach14, Alison Taylor14, Bob C Lin14, Adrian B McDermott14, John R Mascola14, Barney S Graham14. 1. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 2. Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA. 3. Statistical and Data Management Center/Frontier Science Foundation, Brookline, Massachusetts, USA. 4. Departments of Pediatrics and Pharmacy, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA. 5. FHI 360, Durham, North Carolina, USA. 6. Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. 7. Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA. 8. Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (Contractor), Bethesda, Maryland, USA. 9. Department of Pediatrics and Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 10. University of Zimbabwe College of Health Sciences-Clinical Trials Research Centre, Harare, Zimbabwe. 11. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 12. Department of Pediatrics, BronxCare Health Systems, affiliated with Icahn School of Medicine at Mount Sinai, Bronx, New York, USA. 13. University of Florida Center for HIV/AIDS Research, Education and Service, University of Florida College of Medicine, Jacksonville, Florida, USA. 14. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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.
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.
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