Institution: | 1. Department of Internal Medicine III, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany;2. ifi-Institut für interdisziplinäre Medizin/Haus K, Asklepios Klinik St. Georg, Lohmühlenstr. 5, 20099 Hamburg, Germany;3. EPIMED/Vivantes Auguste-Viktoria-Klinikum, Rubensstr. 125, 12157 Berlin, Germany;4. Infectious Diseases Unit, University Medical Centre, Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany;5. Klinik I für Innere Medizin, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany;6. MUC Research GmbH, Karlsplatz 8, 80335 Munich, Germany;g GlaxoSmithKline Vaccines, Rue de l’Institut 89, 1345 Rixensart, Belgium |
Abstract: | The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4+ T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4+ and CD8+ T-cell responses, absolute CD4+ T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4+ T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (p < 0.05). Vaccine-induced HIV-1-specific CD4+ T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8+ T-cells or change in CD8+ T-cell activation marker expression profile was detected. Absolute CD4+ T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4+ T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4+ T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection. |