The REDUC trial's objective is to address one of the core issues with the treatment of HIV, which is that some HIV infected cells hide in so-called latent reservoirs. The reservoirs are unaffected by conventional HIV medication and invisible to the immune system. HDACi have the potential to activate these latently infected cells. This will make the HIV infected cells visible to the immune system; the immune response generate by Vacc-4x will be able to attack and eliminate the infected cells.
The study is divide into two parts. In Part A the safety and tolerability of romidepsin will be evaluated and the effect of romidepsin treatment on HIV-1 transcription in HIV-infected patients virologically suppressed on cART will be determined. In Part B the effect of treatment with Vacc-4x + rhuGM-CSF and romidepsin treatment on the HIV-1 latent reservoir in HIV-infected patients virologically suppressed on cART will be measured. Six patients will be enrolled for part A and the safety and tolerability profile evaluated before enrolling 20 patients in B.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Latency reversing agent
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.
Granulocyte macrophage colony stimulating factor as a local adjuvant
Aarhus University Hospital, Skejby Sygehus
Aarhus N, Denmark
Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Safety and tolerability evaluation as measured by adverse events (AE) and serious adverse events (SAE).
Time frame: 3 weeks
Part B: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus.
Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10\^6 CD4+ T cells). To estimate the frequency of infectious units per 10\^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Blood samples were obtained at Day 0, Day 105 and Day 161.
Time frame: Day 161/175
Part A: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. Estimates of Change From Baseline of the Size of the Latent HIV-1 Reservoir in CD4+ Cells.
Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10\^6 CD4+ T cells). To estimate the frequency of infectious units per 10\^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Total HIV-1 DNA was measured at Day 84
Time frame: Day 56/84
Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Safety and tolerability evaluation of romidepsin and Vacc-4x in combination with GM-CSF as measured by adverse events (AE) and serious adverse events (SAE).
Time frame: 287 days
Part B: Level of HIV-1 Transcription.
At day 105, 112 and 119 patients receive romidepsin and 4 hours after each administration HIV transcription is measured as unspliced HIV-1 RNA.
Time frame: Day 105, 112 and 119
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