Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Antiretrovirals

Federal University of São Paulo

Status and phase: Not yet enrolling; Phase 2

Conditions: Hiv; HIV I Infection

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06805656

SPARC-11

Details and patient eligibility

About

A modern and urgent challenge in fighting HIV infection is to achieve sustained HIV remission without the use of antiretrovirals. The investigators' preliminary data indicate that the use of combined strategies to mitigate the HIV proviral reservoir size among individuals with suppressive antiretroviral treatment achieved unprecedented results in the reduction of HIV DNA present in these cells and in the reduction of CD4 + and CD8 + T cell activation. Combined interventions include intensified antiretroviral treatment to mitigate residual HIV replication, use of a histone deacetylase inhibitor to interrupt viral latency, use of an anti-proliferative medication to reduce long-lived T cells that harbor HIV and a personalized dendritic cell therapy vaccine to eliminate cells with latent HIV infection or cells present in viral sanctuaries. Due to the good results obtained in the exploratory stage of the project, the investigators propose to expand it by recruiting a larger number of patient to confirm the previously obtained results and to generate new insights related to the mechanisms involved in viral latency, latency disruption and the effects of analytical treatment interruption of antiretrovirals among patients undergoing all above mentioned interventions.

Enrollment: 70 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• > 18 years old < 65 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

• 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 (colonystimulating 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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70 participants in 2 patient groups

Antiretroviral Treated (ART) Group

No Intervention group

Description:

Ten patients will receive no further intervention (control group)

ART Intensification Group

Experimental group

Description:

Sixty patients will be included in this stage to undergo the same interventions as Group 6 of the study under registration NCT02961829 of clinicaltrials.gov (antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.), with the adjustment to use also the maraviroc during the first 44 weeks.

Treatment:

Drug: Maraviroc

Drug: Auranofin

Drug: Dolutegravir

Biological: Dendritic Cell Vaccine

Drug: Sirtuin Histone deacetylase inhibitor