A phase I/IIa, multinational, multicentric (IDIBAPS, IRSICAIXA, AARHUS, VUB, APHP), randomised, balanced by centre (to include participants from the 4 arms), open-label, controlled clinical trial. Each participant will be followed up a different time according to study arm: a minimum of 38 weeks in arm I, 31 weeks in arm II, 54 weeks in arm III and 26 weeks in the arm 4. The study duration will be 104 weeks from inclusion of the first participant. Participants will be randomised to one of the following 4 arms: * Arm 1 (study): 14 participants will receive 3 vaccines of HIVARNA01.3 prime, 2 MVA-vectored vaccine boosts, 1 dose of 10-1074 antibodies and 3 doses of romidepsin * Arm 2 (study): 14 participants will receive 5 vaccines of HIVARNA01.3, 1 dose of 10-1074 antibodies and 3 doses of romidepsin * Arm 3 (study): 14 participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 1 dose of 10-1074 antibodies and 3 doses of romidepsin * Arm 4 (control): 14 participants 1 dose of 10-1074 antibodies and 3 doses of romidepsin
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Participants will receive 5 vaccines of placebo of HIVACAR01, 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Grade 3 or above severe local , systemic, clinical or laboratory adverse event t
Local adverse events may be pain, cutaneous reactions including induration and systemic emperature, chills, headache, nausea, vomiting, malaise, and myalgia. Clinical and laboratory must be confirmed at examination or on repeat testing respectively. Any adverse event attributable to the combination therapy leading to discontinuation of the study treatmen
Time frame: 12 days (28 days after each inmuisation)
Proportion of participants who maintain an undetectable viral load
defined as a viral load below the threshold of 50 copies/ml
Time frame: 12 weeks (after discontinuation of antiretroviral therapy)
Percentage of participants with control of viral load below detectable level
Time frame: 24 weeks (after discontinuation of antiretroviral therapy)
Change from baseline in total proviral HIV-1 DNA per 10^6 CD4+ T cells.
Time frame: up to 51 weeks
Change from baseline in integrated proviral HIV-1 DNA per 10^6 CD4+ T cells.
Time frame: up to 51 weeks
Change from baseline in HIV-1 transcription.
According to CA US HIV-1 RNA measured in unfractionated CD4+ T cells
Time frame: up to 39 weeks
Change in plasma HIV-1 RNA from baseline
Time frame: up to 39 weeks
Breadth and magnitude of CD4+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline.
Time frame: up to 27 weeks
Breadth and magnitude of CD8+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline.
Time frame: up to 27 weeks
Breadth and magnitude of CD4+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline.
Time frame: up to 27 weeks
Breadth and magnitude of CD8+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline.
Time frame: up to 27 weeks
Change from baseline in CD8+ T-cell HIV suppressive capacity.
Time frame: up to 51 weeks
Change from baseline in T cell activation markers
Time frame: up to 29 weeks
Change from baseline in T cell activation markers
Time frame: 3 weeeks
Change from baseline in T cell activation markers
Time frame: up to 24 weeks
Change from baseline in T cell subset distribution
Time frame: up to 29 weeks
Change from baseline in T cell subset distribution
Time frame: 14 weeks
Change from baseline in T cell subset distribution
Time frame: up to 27 weeks
Change from baseline in PD-1 expression
Time frame: up to 51 weeks
Evaluate fecal microbiome
Time frame: baseline and at week 14
Characterise viral escape from vaccine-induced immune T cell responses
Comparison of viral sequences pre-cART and rebounding after cART interruption
Time frame: up to 51 weeks
Analysis of changes in sensitivity to neutralisation by 10-1074 of rebounding viruses after cART interruption to identify neutralisation escape mutants.
Time frame: up to 51 weeks
To evaluate mRNA expression profiles in whole PBMC at baseline
Time frame: at first romidepsin administration and 14 and 26 weeks after first romidepsin administration
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