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