TY - JOUR
T1 - Safety, tolerability, and pharmacokinetics of the broadly neutralizing human immunodeficiency virus (HIV)-1 monoclonal antibody VRC01 in HIV-exposed newborn infants
AU - IMPAACT P1112 team
AU - Cunningham, Coleen K.
AU - McFarland, Elizabeth J.
AU - Leavitt Morrison, R.
AU - Capparelli, Edmund V.
AU - Safrit, Jeffrey T.
AU - Mofenson, Lynne M.
AU - Mathieson, Bonnie
AU - Valentine, Megan E.
AU - Perlowski, Charlotte
AU - Smith, Betsy
AU - Hazra, Rohan
AU - Purdue, Lynette
AU - Muresan, Petronella
AU - Harding, Paul A.
AU - Mbengeranwa, Tapiwa
AU - Robinson, Lisa Gaye
AU - Wiznia, Andrew
AU - Theron, Gerhard
AU - Lin, Bob
AU - Bailer, Robert T.
AU - Mascola, John R.
AU - Graham, Barney S.
AU - Aldrovandi, Grace
AU - Bone, Frederic
AU - Dayton, Dale
AU - Johnston, Benjamin
AU - Morgan, Patricia
AU - Myers, Kathryn
AU - Tobin, Nicole
AU - Zimmer, Bonnie
AU - Rossouw, Magdel
AU - Rossouw, Lindie
AU - Louw, Jeanne
AU - Dobroszycki, Joanna
AU - Burey, Marlene
AU - Auguste, Raphaelle
AU - Graham, Kathleen K.
AU - Major-Wilson, Hanna
AU - Mhembere, Tsungai
AU - Maturure, Sukunena
AU - Bwakura-Dangarembizi, Mutsa
AU - Barr, Emily
AU - Dunn, Jennifer
AU - Glenny, Carrie
AU - Chambers, Carrie
AU - Baig, Mahboobullah Mirza
AU - Purswani, Murli
AU - Deville, Jaime G.
AU - Agwu, Allison
AU - Christopher Golden, W.
N1 - Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Background. Although 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. Methods. A 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. Results. Forty 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. Conclusions. Subcutaneous 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.
AB - Background. Although 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. Methods. A 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. Results. Forty 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. Conclusions. Subcutaneous 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.
KW - Broadly neutralizing antibodies
KW - HIV-1
KW - Mother-to-child transmission of HIV
KW - Neonates
KW - VRC01
UR - http://www.scopus.com/inward/record.url?scp=85079561970&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079561970&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiz532
DO - 10.1093/infdis/jiz532
M3 - Review article
C2 - 31681963
AN - SCOPUS:85079561970
SN - 0022-1899
VL - 222
SP - 628
EP - 636
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -