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Abstract
Comparing CD4+ T-cell decline during treatment interruption in HIV-1-infected patients who did or did not receive the candidate immunotherapy Vacc-4x
M.A. Sommerfelt1, F.W.N.M. Wit2, J. Nyhus1, A.-M.B. Kran3, I. Baksaas4, J.M.A. Lange2, B. Sorensen1, D. Kvale3
1Bionor Immuno, Skien, Norway, 2International Antiviral Therapy Evaluation Center (IATEC), Amsterdam, Netherlands, 3Ullevaal University Hospital, Oslo, Norway, 4Mericon, Skien, Norway
Background: This study sought to determine whether the peptide-based immunotherapy candidate, Vacc-4x, targeting dendritic cells of the skin, had influenced CD4+ T cell during a prolonged treatment interruption at the end of the Vacc-4x open-label randomized phase II clinical trial. Since the clinical trial did not include a randomised placebo control arm, Vacc-4x patients were therefore retrospectively compared to similar patients from the Athena cohort that interrupted CART without receiving Vacc-4x. Although Vacc-4x patients are still being followed until they resume CART, this comparative analysis of CD4+ T cell decline encompasses the first 48 weeks following CART interruption.
Methods: Patients were selected from each cohort for the CD4 comparison using the following inclusion criteria: (i) virologically successful CART for a minimum of 6 months prior to treatment interruption (ii) an increase of CD4+ T cells (>150 cells/mm3) experienced during CART. AIDS-defining illness was an exclusion criterion. CD4+ T cell decline was measured for Vacc-4x (n=35) and Athena (n=52) patients. Changes in CD4+ T cell counts were analysed using an ANOVA repeated measurements procedure. The level of significance was set at 0.05 throughout and all p-values obtained were 2-sided.
Results: The Vacc-4x group showed a significantly slower decline in mean CD4+ T cell counts (p<0.0001) over time. Vacc-4x patients had remained CART-free for a median of 70 weeks (17 months) compared to 16 weeks (4 months) for the Athena cohort at the time of analysis.
Conclusions: This study suggests a significant benefit of the Vacc-4x immunotherapy intervention in terms of CD4+ T cell decline following CART interruption. However, these findings should be verified through a randomised prospective placebo-controlled clinical trial. These results nevertheless support the potential for immune-based strategies to sustain immunological fitness during prolonged treatment interruptions – in line with CD4-guided therapy - to reduce exposure to CART and its associated adverse side effects.
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