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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02961829
• Other study ID #: SPARC-7
• Status: Completed
• Phase: N/A
• Start date: July 2015
• Est. completion date: March 2020

Study information

• Verified date: July 2020
• Source: Federal University of São Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2020
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Infection
• HIV

Intervention

Drug:
• Maraviroc
antiretroviral intensification
• Dolutegravir
antiretroviral intensification

Biological:
• Dendritic Cell Vaccine
Therapeutic vaccination

Drug:
• Auranofin
purging
• Sirtuin Histone deacetylase inhibitor
latency disruption

Locations

Country	Name	City	State
Brazil	CCDI	Sao Paulo	SP

Sponsors (4)

Lead Sponsor	Collaborator
Federal University of São Paulo	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado de São Paulo, ViiV Healthcare

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ultrasensitive RNA Viral load,		from baseline and every 4 weeks up to 48 weeks.
Primary	Cell-associated HIV RNA		from baseline and every 4 weeks up to 48 weeks.
Primary	Episomal DNA		from baseline and every 4 weeks up to 48 weeks
Primary	specific HIV antibodies		from baseline and every 4 weeks up to 48 weeks
Primary	CD38 and HLA-DR on CD4 and CD8+ cells		from baseline and every 4 weeks up to 48 weeks
Primary	PBMC for env sequence evolution		from baseline and every 4 weeks up to 48 weeks