DermaVir patch for initial treatment of HIV-infected subjects demonstrates preliminary safety, immunogenicity and HIV-RNA reduction versus placebo immunization
Background: It is a concern that vaccinations paradoxically increase viral load. Therefore, GIEU006 (NCT00711230) was designed to evaluate safety of repeated DermaVir Patch immunizations in antiretroviral-naïve subjects and also test the immunogenicity and antiviral efficacy to guide later development. DermaVir Patch includes a pDNA expressing an HIV (Clade B) virus-like particle formulated into a topically administered synthetic nanomedicine.
Methods: 36 HIV-infected adults (HIV-RNA: 5,000 to 150,000 copies/mL and CD4: ≥400 cells/mm3) were randomized to receive one of three DermaVir doses (0.2, 0.4 or 0.8 mg of pDNA) or placebo at weeks 0, 6, 12 and 18. Standard parameters and HIV(gag)-specific precursor T cells were quantified through week 24. ITT was analyzed by non-parametric statistical tests, the treatment effect with Hodges-Lehmann estimator.
Results: Baseline characteristics were comparable across groups (median age: 38 years; CD4: 506 cells/mm3; HIV-RNA: 20,250 copies/mL; 83% Caucasian; 97% male). No subject stopped vaccinations due to an AE and only one subject initiated ARV. No AE ≥Grade3 occurred, grade 1 and 2 incidences were similar across groups, and only one Grade2 AE was possibly-related to the vaccine. Anti-dsDNA decreased, ANA and CD4 counts did not change and HIV-RNA did not increase. Based on secondary analysis, the 0.4 mg group was superior to others. In this group the HIVgag-specific precursor T cells increased from 5,055 to 9,978 cells/millionPBMC (P=0.07). The median log10 HIV-RNA decreased from 4.5 to 4.0, significantly different from the placebo (P=0.045). The treatment effect compared to placebo at 95% confidence interval was -0.23 (-0.70; 0.09) for log10 HIV-RNA.
Conclusions: DermaVir Patch did not increase viral load nor reduced CD4 counts and was as safe as placebo. Its antiviral and immune-boosting effects in the challenging antiretroviral-naïve setting support further development. The 0.4mg dose emerged as the vaccine candidate for the early treatment of HIV infection.
J. van Lunzen1, R. Pollard2, H.-J. Stellbrink3, A. Plettenberg4, E. Nátz2, Z. Lisziewicz2, R. Freese5, L. Molnár2, S. Calarota6, F. Lori6, J. Lisziewicz2
1Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany, 2Genetic Immunity, Budapest, Hungary, 3ICH Study Center, Hamburg, Germany, 4ifi-Medizin GmbH, Hamburg, Germany, 5CTC North, Hamburg, Hungary, 6ViroStatics srl, Sassari, Italy