Journal Article

Re-boost immunizations with the peptide-based therapeutic HIV vaccine, Vacc-4x, restores geometric mean viral load set-point during treatment interruption

van Lunzen, Jan, Silvia, Nozza, Ökvist, Mats, Asmuth, David, Clotet, Bonaventura, Jolliffe, Darren, Rockstroh, Jürgen K., Krogsgaard, Kim, Podzamczer, Daniel, Pantaleo, Giuseppe, Mitsuyasu, Ronald, Sommerfelt, Maja A., Arastéh, Keikawus, Peters, Barry

2019

Overview

Vacc-4x, a therapeutic HIV vaccine candidate has previously induced a significant reduction in viral load (VL) set-point compared to placebo upon interruption of combination anti-retroviral therapy (ART) (2007/1 study). This study, (2012/1), explored the potential to maintain Vacc-4x effect by re-boosting eligible 2007/1 study participants. Participant inclusion required 2007/1 participants to have completed all Vacc-4x immunizations and interrupted ART for up to 26 weeks. At weeks (wk)0 and 2, participants received intradermal (i.d.) Vacc-4x booster immunizations (1.2mg) on ART with GM-CSF (60μg) i.d. as a local adjuvant. ART was interrupted for up to 16 weeks (wk12-wk28). Participants were then followed on ART until wk36. VL set-point, total proviral DNA (pvDNA) and immunogenicity assessed by IFN-γ ELISPOT, T-cell proliferation and delayed type hypersensitivity (DTH) reactions were compared to participants' values in the 2007/1 study where available. This open, multicenter, clinical study enrolled 33 participants from 9 clinical trial sites in the US and Europe. In the per-protocol (PP) population, the VL set-point geometric mean (GM) 18162 copies/mL was not significantly changed compared to the 2007/1 study (GM VL 22035 copies/mL), (p = 0.453, n = 18). For participants with available preART VL values, the VL set-point (GM 26279 copies/mL) remained significantly lower than the preART VL set-point (GM 74048 copies/mL, p = 0.021, n = 13). A statistically significant reduction in pvDNA (49%) from baseline to wk4 was observed (p = 0.03, n = 26). DTH responses (wk4) increased significantly from baseline (p = 0.006, n = 30) and compared to the 2007/1 study (p = 0.022, n = 29) whilst the proportion of participants with ELISPOT and T-cell proliferation responses was similar between the two studies. Vacc-4x booster immunizations safely maintained the mean VL set-point at that established following primary Vacc-4x therapeutic immunization. The reduction in pvDNA during ART supports the potential for Vacc-4x immunization to reduce HIV reservoirs and thereby contribute to combination HIV cure strategies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adult / AIDS / AIDS vaccines / AIDS Vaccines - administration & dosage / AIDS Vaccines - adverse effects / Analysis / Anti-HIV Agents - administration & dosage / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Biology and Life Sciences / Care and treatment / CD4-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - immunology / Cell proliferation / Clinical trials / Deoxyribonucleic acid / DNA / Drug Administration Schedule / Drug therapy / Enzyme-linked immunosorbent assay / Female / Follow-Up Studies / Gene expression / Granulocyte-macrophage colony-stimulating factor / HIV / HIV infections / HIV Infections - immunology / HIV Infections - therapy / HIV Infections - virology / Hospitals / Human immunodeficiency virus / Humans / Hypersensitivity / Hypersensitivity, Delayed / Immune response / Immunization / Immunization Schedule / Immunization, Secondary - methods / Immunogenicity / Immunotherapy / Infections / Infectious diseases / Interruption / Lymphocyte Activation / Lymphocyte Count / Lymphocytes T / Male / Medical research / Medicine and Health Sciences / Middle Aged / Patient outcomes / Peptides / Prospective Studies / Reduction / Research and Analysis Methods / Safety and security measures / Statistical analysis / Studies / T cells / Treatment Outcome / Vaccines / Viral load / Viral Load - drug effects / Viral Load - immunology / γ-Interferon