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 MD, MSc*; Asmuth, David M. MD; Matining, Roy M. MSc; Spritzler, John ScD; Jacobson, Jeffrey M. MD§; Mailliard, Robbie B. PhD; Li, Xiao-Dong PhD; Martinez, Ana I. RPh; Tenorio, Allan R. MD#; Lori, Franco MD, PhD**; Lisziewicz, Julianna PhD††,‡‡; Yesmin, Suria BS§§; Rinaldo, Charles R. PhD; Pollard, Richard B. MD

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182a99590
Clinical Science
Abstract

Background: 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.

Methods: 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).

Results: 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].

Conclusions: 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.

Author Information

*Division of Infectious Diseases and Center for AIDS Research, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH;

Division of Infectious Diseases, University of California Davis Medical Center, Sacramento, CA;

Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA;

§Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA;

University of Pittsburgh, Pittsburgh, PA;

Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD;

#Department of Medicine, Rush University Medical Center, Chicago, IL;

**ViroStatics srl, Sassari, Italy;

††Genetic Immunity, Budapest, Hungary;

‡‡Genetic Immunity, McLean, VA; and

§§Social & Scientific Systems, Inc, Silver Spring, MD.

Correspondence to: Benigno Rodriguez, MD, MSc, Division of Infectious Diseases and Center for AIDS Research, Case Western Reserve University/University Hospitals of Cleveland, 2061 Cornell Road, Suite 401, Cleveland, OH 44106 (e-mail: rodriguez.benigno@clevelandactu.org).

F.L. is CEO of Virostatics srl; J.L. is CEO of Genetic Immunity; R.B.P. is a consultant and has received financial compensation from Genetic Immunity. NIAID: AI-36219 and AI-069501 (B.R.), AI-68636 and AI-68634 (R.B.M. and J.S.), and 201IC001. SSSS, Inc (ACTG Immunol. Support Lab, D.M.A., X-D.L., and R.B.P.), U01 AI-069471 (A.R.T.). National Office for Research and Technology (Hungary): HIKC05 and DVCLIN01 (J.L.).

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Received September 12, 2012

Accepted August 04, 2013

© 2013 by Lippincott Williams & Wilkins