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

• Status: Completed
• Trial end date: 2020-03-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Federal University of São Paulo
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico; Fundação de Amparo à Pesquisa do Estado de São Paulo; ViiV Healthcare
• Treatments: Auranofin; Dolutegravir; Histone Deacetylase Inhibitors; Maraviroc; Niacin; Niacinamide; Nicotinic Acids; Vaccines

Criteria

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.