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DermaVir as a therapeutic vaccination strategy for HIV infection: results from ACTG protocol A5176
Abstract Content:
Background: DermaVir candidate therapeutic vaccine is a topically-administered pDNA-nanomedicine expressing HIV(CladeB) virus-like particles consisting of 15 antigens.
Methods: Treated HIV-infected adults (VL< 50, CD4>350) were randomized to placebo or three increasing DermaVir doses, n=5-6 evaluable subjects/group. Analyses were exploratory and not powered for immunogenicity. Both lower-dose groups received DermaVir at weeks 1/7/13; the highest-dose group at weeks 0/1/6/7/12/13. Results (*p< 0.2; **p< 0.1) are median SFU/million cells, of standard overnight and cultured IFN-γ ELISPOT assays, at baseline and post-vaccine time-points (PVT) 9/17/37 weeks, using one Tat/Rev and three overlapping Gag peptide pools (p17, p24, p15). The cultured assay detects HIV-specific precursor T-cells with high proliferative capacity (PHPC).
Results: Groups were comparable. Standard ELISPOT responses at PVTs tended to be higher in the combined DermaVir vs. the placebo group for p17 (weeks 9, 17, 37: 220 vs. 165, 213 vs. 207, 247 vs. 56), p24 (316 vs. 95*, 267 vs. 168, 305 vs. 28**), and p15 (119 vs. 92, 95 vs. 102, 112 vs. 95), but not Tat/Rev (23 vs. 45, 20 vs. 18, 13 vs. 29). PHPC responses showed a similar pattern at weeks 9 and 17 to p24 (1635 vs. 813, 2179 vs. 701* and 2427 vs. 294**), p15 (947 vs. 833, 2055 vs. 1352, 285 vs. 892) and Tat/Rev (566 vs. 84, 232 vs. 22, 0 vs. 35). Both assays showed a similar trend toward higher responses in the DermaVir group comparing AUCs (p≥0.18). The above differences were not statistically significant. The within-subject maximum PHPC AUC (weeks 0-37) of the three Gag pools was significantly greater in the intermediate-dose group (0.4 mg pDNA) vs. the placebo group (p=0.03).
Conclusions: DermaVir showed a trend toward greater HIV-specific T-cell responses in virologically-suppressed patients. The medium DermaVir dose tended to show the greatest effect, consistent with two previous studies in different HIV-infected patient populations.
Methods: Treated HIV-infected adults (VL< 50, CD4>350) were randomized to placebo or three increasing DermaVir doses, n=5-6 evaluable subjects/group. Analyses were exploratory and not powered for immunogenicity. Both lower-dose groups received DermaVir at weeks 1/7/13; the highest-dose group at weeks 0/1/6/7/12/13. Results (*p< 0.2; **p< 0.1) are median SFU/million cells, of standard overnight and cultured IFN-γ ELISPOT assays, at baseline and post-vaccine time-points (PVT) 9/17/37 weeks, using one Tat/Rev and three overlapping Gag peptide pools (p17, p24, p15). The cultured assay detects HIV-specific precursor T-cells with high proliferative capacity (PHPC).
Results: Groups were comparable. Standard ELISPOT responses at PVTs tended to be higher in the combined DermaVir vs. the placebo group for p17 (weeks 9, 17, 37: 220 vs. 165, 213 vs. 207, 247 vs. 56), p24 (316 vs. 95*, 267 vs. 168, 305 vs. 28**), and p15 (119 vs. 92, 95 vs. 102, 112 vs. 95), but not Tat/Rev (23 vs. 45, 20 vs. 18, 13 vs. 29). PHPC responses showed a similar pattern at weeks 9 and 17 to p24 (1635 vs. 813, 2179 vs. 701* and 2427 vs. 294**), p15 (947 vs. 833, 2055 vs. 1352, 285 vs. 892) and Tat/Rev (566 vs. 84, 232 vs. 22, 0 vs. 35). Both assays showed a similar trend toward higher responses in the DermaVir group comparing AUCs (p≥0.18). The above differences were not statistically significant. The within-subject maximum PHPC AUC (weeks 0-37) of the three Gag pools was significantly greater in the intermediate-dose group (0.4 mg pDNA) vs. the placebo group (p=0.03).
Conclusions: DermaVir showed a trend toward greater HIV-specific T-cell responses in virologically-suppressed patients. The medium DermaVir dose tended to show the greatest effect, consistent with two previous studies in different HIV-infected patient populations.