Background:
HVRRICANE is a phase I, proof of concept, open-label, randomized clinical trial to evaluate safety, immunogenicity and efficacy in HIV reservoir reduction of a prime-boost strategy with a multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS DNA) and modified vaccinia Ankara Chiang Mai Double Recombinant (MVA-CMDR) vaccine ± co-administration of Toll-like Receptor 4 agonist (within Cervarix® human papilloma vaccine) in adolescents and youth living with perinatally acquired HIV-1.
Methods:
Twenty-five South African adolescents living with perinatal HIV, 14 to 16 years of age were enrolled. All started antiretroviral therapy prior to 6 months of age, with continuous viral suppression through enrollment, and randomized to HIV vaccines only (n=10, Arm 1), HIV vaccines and Cervarix® (n=10, Arm 2) or Cervarix® only (n=5, Arm 3). The HIV DNA vaccines were administered through a needle free device (PharmaJet Stratis®) at weeks 0 and 4 ± Cervarix® and the MVA-CMDR at 24 (± Cervarix®) and 36 weeks (MVA-CMDR only). Local and systemic reactions were captured 30 minutes after vaccination and on diary cards for seven days. Pregnancy was screened at each visit.
Results:
Two participants missed week 24 immunization (due to TB and pregnancy). There were no loss to follow up, no deaths and 15 participants have completed their week 60 visits. Local and systemic reactogenicity reported as mild or moderate in all 25 participants: 24 (96%) had local and 21 (84%) systemic reactions. Five participants with severe reactogenicity all reduced to moderate, mild or resolved within 2 days. There was one serious adverse event (SAE) and 2 adverse events (AEs) above Grade 2, all in Arm 2. The SAE (acute appendicitis) was unrelated to study participation. One Grade 3 AE (reduced estimated glomerular filtration rate) was considered tenofovir- and not vaccine-related. The other Grade 3 AE was headache for 10 days that was severe on days 1 and 2. A pregnancy during the study was noted (Arm 2) and was electively terminated. The first MVA-CMDR vaccine was omitted due to the pregnancy, but the final CMDR was given after termination. No vaccine related AE prompted discontinuation of investigational product. All participants are expected to complete the study by mid-October 2023.
Conclusions:
This study represents the first combined therapeutic HIV vaccine study in pediatrics. While all participants reported local and/or systemic reactions to vaccination, most events were self-limiting and no dose limiting AEs were reported.
