Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x:a phase 2 randomised, double-blind, placebo-controlled trial

BACKGROUND: Present combination antiretroviral therapy (cART) alone does not cureHIV infection and requires lifelong drug treatment. The potential role of HIVtherapeutic vaccines as part of an HIV cure is under consideration. Our aim wasto assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-basedHIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adultsinfected with HIV-1.METHODS: Between July, 2008, and June, 2010, we did a multinational double-blind,randomised, phase 2 study comparing Vacc-4x with placebo. Participants wereadults infected with HIV-1 who were aged 18-55 years and virologically suppressedon cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 10(6) cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, theUK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo.Group allocation was masked from participants and investigators. Four primaryimmunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were givenintradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. Thecoprimary endpoints were cART resumption and changes in CD4 counts duringtreatment interruption. Analyses were by modified intention to treat: allparticipants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed.The 52 week follow-up period was completed in June, 2011. For the coprimaryendpoints the proportion of participants who met the criteria for cART resumptionwas analysed with a logistic regression model with the treatment effect beingassessed in a model including country as a covariate. This study is registeredwith ClinicalTrials.gov, number NCT00659789.FINDINGS: 174 individuals were screened; because of slow recruitment, enrolmentstopped with 136 of a planned 345 participants and 93 were randomly assigned toreceive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stoppedcART at week 28. Of the participants who resumed cART, 30 (34%) were in theVacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23,100 copies per mL Vacc-4x vs 71,800 copies permL placebo; p=0·025) and week 52 (median 19,550 copies per mL vs 51,000 copiesper mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic,inducing proliferative responses in both CD4 and CD8 T-cell populations.INTERPRETATION: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit ofvaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worthconsideration in future HIV-cure investigative strategies