The HIV-1 vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional cross-reactive CD4+ T-cell responses in healthy HIV-1-seronegative volunteers [8]. This study evaluated the safety and immunogenicity of F4/AS01 in HIV-1-infected ART-experienced and ART-naïve individuals. F4/AS01 (GlaxoSmithKline Vaccines, Rixensart, Belgium) contains 10 μg recombinant fusion protein F4 adjuvanted SCR7 mw with AS01B[8]. F4 is produced in Escherichia coli and

comprises 4 full-length HIV-1 clade B antigens: p24 (BH10), RT (HXB2), Nef (Bru-Lai) and p17 (BH10). AS01B is an Adjuvant System containing 50 μg 3-O-desacyl-4′-monophosphoryl lipid A (MPL), 50 μg QS-21 (Quillaja saponaria Molina, fraction 21; Antigenics Inc., a wholly owned subsidiary of Agenus Inc., Lexington MA, USA) and liposomes. This Phase I, randomised, observer-blind, placebo-controlled trial was conducted at 6 centres in Germany in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines [9]. The study was approved by the local independent ethics committee and the German regulatory authority. All subjects provided written informed consent. The primary objective was to evaluate the reactogenicity and safety of the vaccine. Secondary objectives included

assessment of HIV-1-specific CD4+ T-cell responses, CD4+ T-cell count and HIV-1 viral load. HIV-1-specific CD8+ T-cell responses and humoral immune responses to F4 and its component antigens were assessed C59 purchase as exploratory objectives. HIV-1 infected adults aged 18–55 years with stable, asymptomatic HIV-1 infection and CD4+ T-cell count ≥450 cells/mm3 were eligible. ART-experienced subjects must have been stable on ART for ≥1 year with an undetectable viral load (<50 copies/ml HIV-1 RNA) on two occasions at least 3 months apart during the 6 months prior to enrolment. ART-naïve subjects

had to have a viral load of 5000–80,000 copies/ml at screening. Other Tolmetin standard eligibility criteria were used for enrolment [9]. ART-naïve subjects were only enrolled after a planned review of safety data from the ART-experienced cohort. In each cohort, subjects were randomised (1:1) to receive two doses of F4/AS01 or 0.9% saline (placebo) intramuscularly (deltoid, non-dominant arm) 1-month apart. Randomisation was performed using a central internet-based system. In ART-naïve subjects, randomisation took into account viral load at screening (<40,000 or ≥40,000 copies/ml). Subjects were followed for 12 months post-dose 1. Blood samples for assessment of cell-mediated immune and antibody responses were obtained before vaccination, 2 weeks post-dose 2 and at month 4 and 12. CD4+ T-cell count, viral load and haematology/biochemistry were monitored throughout the study period. All laboratory assays were performed blinded.