Safety, tolerability, and immunogenicity of repeated doses of dermavir, a candidate therapeutic HIV vaccine, in HIV-infected patients receiving combination antiretroviral therapy

results of the ACTG 5176 trial.

Benigno Rodriguez, David Asmuth, Roy M. Matining, John Spritzler, Jeffrey M. Jacobson, Robbie B. Mailliard, Xiao Dong Li, Ana I. Martinez, Allan R. Tenorio, Franco Lori, Julianna Lisziewicz, Suria Yesmin, Charles R. Rinaldo, Richard B Pollard

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

HIV-specific cellular immune responses are associated with control of viremia and delayed disease progression. An effective therapeutic vaccine could mimic these effects and reduce the need for continued antiretroviral therapy. DermaVir, a topically administered plasmid DNA-nanomedicine expressing HIV (CladeB) virus-like particles consisting of 15 antigens, induces predominantly central memory T-cell responses. Treated HIV-infected adults (HIV RNA <50 and CD4 >350) were randomized to placebo or escalating DermaVir doses (0.1 or 0.4 mg of plasmid DNA at weeks 1, 7, and 13 in the low- and intermediate-dose groups and 0.8 mg at weeks 0, 1, 6, 7, 12, and 13 in the high-dose group), n = 5-6 evaluable subjects per group. Immunogenicity was assessed by a 12-day cultured interferon-γ enzyme-linked immunosorbent spot assay at baseline and at weeks 9, 17, and 37 using 1 Tat/Rev and 3 overlapping Gag peptide pools (p17, p24, and p15). Groups were comparable at baseline. The study intervention was well tolerated, without dose-limiting toxicities. Most responses were highest at week 17 (4 weeks after last vaccination) when Gag p24 responses were significantly greater among intermediate-dose group compared with control subjects [median (IQR): 67,600 (5633-74,368) versus 1194 (9-1667)] net spot-forming units per million cells, P = 0.032. In the intermediate-dose group, there was also a marginal Gag p15 response increase from baseline to week 17 [2859 (1867-56,933), P = 0.06], and this change was significantly greater than in the placebo group [0 (-713 to 297), P = 0.016]. DermaVir administration was associated with a trend toward greater HIV-specific, predominantly central memory T-cell responses. The intermediate DermaVir dose tended to show the greatest immunogenicity, consistent with previous studies in different HIV-infected patient populations.

Original languageEnglish (US)
Pages (from-to)351-359
Number of pages9
JournalJournal of acquired immune deficiency syndromes (1999)
Volume64
Issue number4
StatePublished - Dec 1 2013

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AIDS Vaccines
HIV
Safety
Plasmids
Therapeutics
Placebos
Nanomedicine
T-Lymphocytes
Viremia
DNA
Cellular Immunity
Virion
Interferons
Disease Progression
DermaVir
Vaccination
Vaccines
Enzyme-Linked Immunosorbent Assay
RNA
Antigens

ASJC Scopus subject areas

  • Medicine(all)

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Safety, tolerability, and immunogenicity of repeated doses of dermavir, a candidate therapeutic HIV vaccine, in HIV-infected patients receiving combination antiretroviral therapy : results of the ACTG 5176 trial. / Rodriguez, Benigno; Asmuth, David; Matining, Roy M.; Spritzler, John; Jacobson, Jeffrey M.; Mailliard, Robbie B.; Li, Xiao Dong; Martinez, Ana I.; Tenorio, Allan R.; Lori, Franco; Lisziewicz, Julianna; Yesmin, Suria; Rinaldo, Charles R.; Pollard, Richard B.

In: Journal of acquired immune deficiency syndromes (1999), Vol. 64, No. 4, 01.12.2013, p. 351-359.

Research output: Contribution to journalArticle

Rodriguez, Benigno ; Asmuth, David ; Matining, Roy M. ; Spritzler, John ; Jacobson, Jeffrey M. ; Mailliard, Robbie B. ; Li, Xiao Dong ; Martinez, Ana I. ; Tenorio, Allan R. ; Lori, Franco ; Lisziewicz, Julianna ; Yesmin, Suria ; Rinaldo, Charles R. ; Pollard, Richard B. / Safety, tolerability, and immunogenicity of repeated doses of dermavir, a candidate therapeutic HIV vaccine, in HIV-infected patients receiving combination antiretroviral therapy : results of the ACTG 5176 trial. In: Journal of acquired immune deficiency syndromes (1999). 2013 ; Vol. 64, No. 4. pp. 351-359.
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abstract = "HIV-specific cellular immune responses are associated with control of viremia and delayed disease progression. An effective therapeutic vaccine could mimic these effects and reduce the need for continued antiretroviral therapy. DermaVir, a topically administered plasmid DNA-nanomedicine expressing HIV (CladeB) virus-like particles consisting of 15 antigens, induces predominantly central memory T-cell responses. Treated HIV-infected adults (HIV RNA <50 and CD4 >350) were randomized to placebo or escalating DermaVir doses (0.1 or 0.4 mg of plasmid DNA at weeks 1, 7, and 13 in the low- and intermediate-dose groups and 0.8 mg at weeks 0, 1, 6, 7, 12, and 13 in the high-dose group), n = 5-6 evaluable subjects per group. Immunogenicity was assessed by a 12-day cultured interferon-γ enzyme-linked immunosorbent spot assay at baseline and at weeks 9, 17, and 37 using 1 Tat/Rev and 3 overlapping Gag peptide pools (p17, p24, and p15). Groups were comparable at baseline. The study intervention was well tolerated, without dose-limiting toxicities. Most responses were highest at week 17 (4 weeks after last vaccination) when Gag p24 responses were significantly greater among intermediate-dose group compared with control subjects [median (IQR): 67,600 (5633-74,368) versus 1194 (9-1667)] net spot-forming units per million cells, P = 0.032. In the intermediate-dose group, there was also a marginal Gag p15 response increase from baseline to week 17 [2859 (1867-56,933), P = 0.06], and this change was significantly greater than in the placebo group [0 (-713 to 297), P = 0.016]. DermaVir administration was associated with a trend toward greater HIV-specific, predominantly central memory T-cell responses. The intermediate DermaVir dose tended to show the greatest immunogenicity, consistent with previous studies in different HIV-infected patient populations.",
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