Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure

Sponsor

Federal University of São Paulo (Other)

Overall Status

Completed

CT.gov ID

NCT02961829

Collaborator

Fundação de Amparo à Pesquisa do Estado de São Paulo (Other), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other), ViiV Healthcare (Industry)

Enrollment

Location

Arms

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

It is becoming clear that a combination of interventions will be desirable to achieve HIV cure. Therefore the investigators propose a pilot proof of concept study, using combination of a number of different interventions for eradicating residual plasma viremia and decreasing HIV reservoirs. The investigators hypothesize that, (i) antiretroviral intensification using Maraviroc, and/or dolutegravir with (ii) Dendritic Cell vaccination using autologous HIV, and (iii) purging intervention using the Class III HDACs, Sirtuin-1, and (iv) decreasing the ratio of long-lived central memory (TCM)/transitional memory (TTM) CD4+ T-cells using Auranofin will provide a synergistic impact leading to a sterilizing cure of HIV infection. Results of this study may provide insightful evidence for planning the next steps using the more efficacious combination of intervention strategies towards HIV sterilizing cure.

Condition or Disease	Intervention/Treatment	Phase
Chronic Infection HIV	Drug: Maraviroc Drug: Dolutegravir Biological: Dendritic Cell Vaccine Drug: Auranofin Drug: Sirtuin Histone deacetylase inhibitor	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure

Actual Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Mar 1, 2019

Actual Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Antiretroviral Treated (ART) Group Five patients will receive no further intervention this group (control group)
Experimental: ART Intensification Group Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks	Drug: Maraviroc antiretroviral intensification Other Names: Selzentry Celsentri Drug: Dolutegravir antiretroviral intensification Other Names: Tivicay
Experimental: ART Intensification + Nicotinamide Group Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.	Drug: Maraviroc antiretroviral intensification Other Names: Selzentry Celsentri Drug: Dolutegravir antiretroviral intensification Other Names: Tivicay Drug: Sirtuin Histone deacetylase inhibitor latency disruption Other Names: Nicotinamide
Experimental: ART Intensification + Auranofin Group Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.	Drug: Maraviroc antiretroviral intensification Other Names: Selzentry Celsentri Drug: Dolutegravir antiretroviral intensification Other Names: Tivicay Drug: Auranofin purging Other Names: Gold Salt
Experimental: ART Intensification + DC vaccine Group Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.	Drug: Dolutegravir antiretroviral intensification Other Names: Tivicay Biological: Dendritic Cell Vaccine Therapeutic vaccination Other Names: DC Vaccine
Experimental: Multi Interventional Group Five patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.	Drug: Dolutegravir antiretroviral intensification Other Names: Tivicay Biological: Dendritic Cell Vaccine Therapeutic vaccination Other Names: DC Vaccine Drug: Auranofin purging Other Names: Gold Salt Drug: Sirtuin Histone deacetylase inhibitor latency disruption Other Names: Nicotinamide

Outcome Measures

Primary Outcome Measures

Ultrasensitive RNA Viral load, [from baseline and every 4 weeks up to 48 weeks.]
Cell-associated HIV RNA [from baseline and every 4 weeks up to 48 weeks.]
Episomal DNA [from baseline and every 4 weeks up to 48 weeks]
specific HIV antibodies [from baseline and every 4 weeks up to 48 weeks]
CD38 and HLA-DR on CD4 and CD8+ cells [from baseline and every 4 weeks up to 48 weeks]
PBMC for env sequence evolution [from baseline and every 4 weeks up to 48 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years old Documented HIV-1 infection.
Has voluntarily signed ICF.
On HAART ≥ 2 years, without changes in the 24 weeks immediately prior to screening.
HIV viral load <50 copies/mL, and never > 50 copies/mL on 2 consecutive occasions in the last 2 years. CD4 count nadir.
350 cells/ mm3 Current CD4 count > 500 cells/ mm3.
R5 HIV-1 at Screening as defined by proviral DNA genotropism.

Exclusion Criteria:

A subject will NOT be eligible for study participation if he/she meets ANY of the following criteria:

Any evidence of an active AIDS-defining condition.
Any significant acute medical illness in the past 8 weeks.
Women who are pregnant or breastfeeding.
Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy; investigational agents; immunomodulators (colony-stimulating factors, growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons); coumadin, warfarin, or other Coumadin derivative anticoagulants. Use of an agent definitely or possibly associated with effects on QT intervals: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid or nicotinamide within the last 30 days. Potential participants may enroll after a 30-day washout period.
Known hypersensitivity to the components of gold salt, nicotinamide or its analogs.
Hepatitis B (HBsAg +) or Hepatitis C (HCV RNA +) infection.
Known renal insufficiency defined as calculated creatinine clearance (Cockcroft Gault formula) <60 mL/min.
Subjects with a laboratory abnormality grade 3 or 4 with the following exceptions: pancreatic amylase, cholesterol, triglyceride, gamma glutamyl transpeptidase, bilirubin.
Any condition which, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.