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

Federal University of São Paulo

Status: Completed

Conditions: HIV; Chronic Infection

Treatments: Drug: Maraviroc; Drug: Sirtuin Histone deacetylase inhibitor; Drug: Dolutegravir; Drug: Auranofin; Biological: Dendritic Cell Vaccine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02961829

SPARC-7

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 6 patient groups

Antiretroviral Treated (ART) Group

No Intervention group

Description:

Five patients will receive no further intervention this group (control group)

ART Intensification Group

Experimental group

Description:

Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks

Treatment:

Drug: Dolutegravir

Drug: Maraviroc

ART Intensification + Nicotinamide Group

Experimental group

Description:

Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.

Treatment:

Drug: Sirtuin Histone deacetylase inhibitor

Drug: Dolutegravir

Drug: Maraviroc

ART Intensification + Auranofin Group

Experimental group

Description:

Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.

Treatment:

Drug: Auranofin

Drug: Dolutegravir

Drug: Maraviroc

ART Intensification + DC vaccine Group

Experimental group

Description:

Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.

Treatment:

Biological: Dendritic Cell Vaccine

Drug: Dolutegravir

Multi Interventional Group

Experimental group

Description:

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.

Treatment:

Biological: Dendritic Cell Vaccine

Drug: Auranofin

Drug: Sirtuin Histone deacetylase inhibitor

Drug: Dolutegravir