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
Elizabeth J. McFarland, Coleen K. Cunningham, Petronella Muresan, Edmund V. Capparelli, Charlotte Perlowski, Patricia Morgan, Betsy Smith, Rohan Hazra, Lynette Purdue, Paul A. Harding, Gerhard Theron, Hilda Mujuru, Allison L. Agwu, Murli Purswani, Mobeen H. Rathore, Britta Flach, Alison Taylor, Bob C. Lin, Adrian B. McDermott, John R. Mascola, Barney S. Graham, Magdel Rossouw, Lindie Rossouw, Jeanne Louw, Tichaona Vhembo, Tsungai Mhembere, Petronella Matibe, Saniyyah Mahmoudi, Alexandrea Maldonado, Nizar Maraqa, Mahboobullah Mirza Baig, Tanya Rogo, Martha Cavallo, Aleisha Collinson-Streng, Thuy Anderson, W. Christopher Golden, Deborah Persaud, Ana M. Puga, Lisa-Gaye Robinson, Zulma Eysallenne, Dayana Leon, Mary E. Paul, Chivon McMullen-Jackson, Shelley Buschur, Mariam Pontifes, Joyce Sung, Carrie Glenny, Jennifer Dunn, Kacey Navarro
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.