Indicators of therapeutic vaccine effect using GTU-MultiHIV B clade DNA in treatment-naïve subtype C HIV-1 infected subjects
Presented by Eftyhia Vardas (South Africa).
E. Vardas1, I. Stanescu2, M. Valtavaara2, T. Kuntonen3, C. Gray4, M. Leionen3, M. Ustav2, K. Reijonen2
1Ndlela Research and Clinical Trials, Johannesburg, South Africa, 2FIT Biotech, Tampere, Finland, 34Pharma, Turku, Finland, 4National Institute for Communicable Diseases, Johannesburg, South Africa
Background: Therapeutic vaccination is an important adjunct to the management of HIV infected individuals to decrease transmission and slow down progression of disease.The final report using a plasmid DNA comprising complete sequences of Rev, Nef, Tat, p17/p24 proteins, and epitope stretch of previously identified T cell epitopes in pol and env of a subtype B-HIV-1 Han-2 isolate is presented.
Methods: 60 subtype C HIV-1 infected individuals with CD4 counts ³350 x 106/L and viral loads ³50 copies/ml at screening were randomly allocated to vaccine or placebo at 2:1 and received either ID(0.5 mg/dose) or IM(1 mg/dose) immunizations using the Biojector. Vaccinations were administered at 0, 1 and 3 months, with boosts at 19 and 20 months with 1 mg/dose (ID) and 2 mg/dose (IM). Efficacy endpoints were viral loads and CD4 counts. Immunogenicity was evaluated using IFN-g ELISPOT reactivity to B and C consensus peptide pools. HLA typing was performed with sequence-based typing (SBT).
Results: IM vaccine delivery resulted in a significant increase in CD4 counts (p=0.013) and a 0.5 log decrease in viraemia (p=0.002) at 108 weeks of follow-up. Vaccine effect was emphasized by a decrease in viral load and increase in CD4 after boosting at 64 weeks. HLA typing also supported the vaccine effect after the exclusion of known HLA types which are associated with slower progression. T cell responses recognizing Gag and CTL epitopes in B and C peptide pools were observed after ID vaccination rather than IM. There were no vaccine related serious adverse events and mild to moderate reactogenicity.
Conclusions: There was a significant reduction in viral load and increased CD4 counts after IM vaccination. The concept was further demonstrated by responses after boosting and in data controlled for HLA type. The investigational HIV-1 vaccine, GTU®-MultiHIV B clade is safe and well tolerated and has demonstrated clinical effect
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