Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU®-Multi-HIVB, in untreated HIV-1 infected subjects

• Published in: Vaccine Vol. 30; no. 27; pp. 4046 - 4054
• Main Authors: Vardas, Eftyhia, Stanescu, Ioana, Leinonen, Mika, Ellefsen, Kim, Pantaleo, Giuseppe, Valtavaara, Minna, Ustav, Mart, Reijonen, Kalevi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 08.06.2012; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - therapy; Acquired Immunodeficiency Syndrome - virology; Adult; adults; AIDS; AIDS Vaccines - administration & dosage; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; Allergy and Immunology; antiretroviral agents; Antiretroviral drugs; CD4 Lymphocyte Count; CD4-positive T-lymphocytes; CD8-positive T-lymphocytes; Chronic HIV-1; cytokines; Deoxyribonucleic acid; disease course; DNA; Drug-Related Side Effects and Adverse Reactions - epidemiology; Female; genes; Genotype; haplotypes; HIV; HIV infections; HIV-1 - classification; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; immune response; immunization; Immunotherapy - methods; Injections, Intradermal; Injections, Intramuscular; Male; monitoring; morbidity; mortality; Placebos - administration & dosage; plasmids; Plasmids - administration & dosage; recombinant DNA; recombinant vaccines; RNA, Viral - blood; screening; South Africa; Therapeutic HIV-1 vaccines; Treatment Outcome; Untreated; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Viral Load; Young Adult; South Africa; South Africa; Untreated; Chronic HIV-1; Therapeutic HIV-1 vaccines
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2012.04.007

► FIT GTU®-multi-HIVB was the first therapeutic HIV-1 vaccine trial conducted in South Africa. ► This plasmid DNA vaccine is safe and well-tolerated in HIV-1 infected, anteretrovial naive subjects. ► Cross subtype reactivity of subtype B derived vaccine in subtype C infected subjects was shown. ► Significant CD4 increases and VL decreases after IM vaccine were maintained for more than 2 years. ► This DNA HIV vaccine may be used as affordable prime/boost regimens alone or as an adjunct to HAART. Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU®-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate. 63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4≥350cells/mm3 and pHIV-RNA≥50copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5mg/dose) or intramuscularly (IM) (1mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1mg/dose (ID) and 2mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts. Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in logpHIV-RNA (p=0.012) and increases in CD4+ T cell counts (p=0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation. The GTU®-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801haplotypes.