Subcutaneous doses of a broadly neutralizing monoclonal antibody, known as VRC01LS, given at birth and 12 weeks were well-tolerated by HIV-exposed infants, according to the results of an open-label safety and pharmacokinetic study presented at the Conference on Retroviruses and Opportunistic Infections. Researchers are studying VRC01LS in combination with ART to prevent HIV infection in neonates.
Elizabeth J. McFarland, MD, medical director of Children’s Hospital Colorado’s HIV program and professor of pediatrics at the University of Colorado School of Medicine, said at a press conference that passive immunization with a broadly neutralizing monoclonal antibody has successfully been used to prevent hepatitis B, and neutralizing antibodies are also used to prevent respiratory syncytial virus infection in infants.
In the study, if infants were not breastfed (n = 10), they received a subcutaneous dose of VRC01LS (80 mg for birth weights 2 kg to 4.5 kg) within 72 hours of birth. If infants were breastfed (n = 11), the first dose was administered subcutaneously within 5 days of birth, and a second dose (100 mg) was given subcutaneously at week 12 if the infant was still breastfeeding.
In addition to VRC01LS, all mothers and infants included in the study also received ART.
“Infant transmission was a potentially very ideal setting for the use of monoclonal antibody because it could be given at the time of birth and then periodically during the first year of life,” McFarland said. “Breastfeeding exposure is a defined and known time frame, so using antibody in that setting could be a potentially terrific adjunct to ART, which we know is difficult to take and there are issues with adherence.”
The researchers reported that VRC01LS was well-tolerated among infants, and no treatment-related toxicities classified as greater than grade 2 occurred. Local reactions were reported for 50% of nonbreastfeeding infants and 82% of breastfeeding infants after the first dose, and all were either grade 1 or 2. Most (95%) reactions resolved within 24 hours. Reactions occurred less frequently after the second dose (20%).
McFarland and colleagues observed that subcutaneous administration of the antibody resulted in rapid absorption, and all plasma levels on day 1 were more than 100 µg /mL.
VRC01LS is a modified version of the antibody VRC01, which has been under investigation as well. McFarland and colleagues found that plasma levels were significantly greater in infants receiving VRC01LS on day 28 and day 56 compared with VRC01, even though lower weight-band dosing was used for VRC01LS (20-32 mg/kg vs. 40 mg/kg). The researchers noted that the median VRC01LS plasma level at week 12 was 39.1 µg/mL. All infants had plasma levels greater than 20 µg/mL.
“This monoclonal antibody could potentially be given about every 12 weeks, which would potentially be very feasible during the first year of life when breastfeeding exposure is occurring,” McFarland said.
By Katherine Bortz
McFarland EJ, et al. Abstract 45. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.