Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
Not Applicable
Completed
- Conditions
- HIVChronic Infection
- Interventions
- Biological: Dendritic Cell VaccineDrug: Sirtuin Histone deacetylase inhibitor
- Registration Number
- NCT02961829
- Lead Sponsor
- Federal University of São Paulo
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 30
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ART Intensification Group Maraviroc Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks ART Intensification + Nicotinamide Group Maraviroc Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks. ART Intensification + Nicotinamide Group Sirtuin Histone deacetylase inhibitor Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks. ART Intensification + DC vaccine Group Dendritic Cell Vaccine Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine. Multi Interventional Group Dolutegravir 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. Multi Interventional Group Dendritic Cell Vaccine 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. Multi Interventional Group Auranofin 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. Multi Interventional Group Sirtuin Histone deacetylase inhibitor 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. ART Intensification + Nicotinamide Group Dolutegravir Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks. ART Intensification Group Dolutegravir Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks ART Intensification + DC vaccine Group Dolutegravir Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine. ART Intensification + Auranofin Group Auranofin Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks. ART Intensification + Auranofin Group Maraviroc Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks. ART Intensification + Auranofin Group Dolutegravir Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
- Primary Outcome Measures
Name Time Method 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. specific HIV antibodies from baseline and every 4 weeks up to 48 weeks Episomal DNA 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
CCDI
🇧🇷Sao Paulo, SP, Brazil