Journal Article

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

Stanescu, Ioana, Vardas, Eftyhia, Leinonen, Mika, Pantaleo, Giuseppe, Ustav, Mart, Valtavaara, Minna, Ellefsen, Kim, Reijonen, Kalevi

2012

Overview

► 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: 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