Clinical trial NCT02961829: Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
Official title: Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Infection
HIV
Keywords: Dendritic Cell vaccination using
antiretroviral intensification
Auranofin
Histone Deacetylase Inhibitor
residual viral replication
HIV sanctuaries
HIV latency
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
name: ViiV Healthcare
First posted: 2016-11-11
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Ultrasensitive RNA Viral load,
timeFrame: from baseline and every 4 weeks up to 48 weeks.
measure: Cell-associated HIV RNA
timeFrame: from baseline and every 4 weeks up to 48 weeks.
measure: Episomal DNA
timeFrame: from baseline and every 4 weeks up to 48 weeks
measure: specific HIV antibodies
timeFrame: from baseline and every 4 weeks up to 48 weeks
measure: CD38 and HLA-DR on CD4 and CD8+ cells
timeFrame: from baseline and every 4 weeks up to 48 weeks
measure: PBMC for env sequence evolution
timeFrame: from baseline and every 4 weeks up to 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: CCDI
state: SP
Study officials:
References:
citation: de Almeida Baptista MV, da Silva LT, Samer S, Oshiro TM, Shytaj IL, Giron LB, Pena NM, Cruz N, Gosuen GC, Ferreira PRA, Cunha-Neto E, Galinskas J, Dias D, Sucupira MCA, de Almeida-Neto C, Salomao R, da Silva Duarte AJ, Janini LM, Hunter JR, Savarino A, Juliano MA, Diaz RS. Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial. AIDS Res Ther. 2022 Jan 12;19(1):2. doi: 10.1186/s12981-021-00426-z.
citation: Diaz RS, Shytaj IL, Giron LB, Obermaier B, Della Libera E Jr, Galinskas J, Dias D, Hunter J, Janini M, Gosuen G, Ferreira PA, Sucupira MC, Maricato J, Fackler O, Lusic M, Savarino A; SPARC Working Group. Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial. Int J Antimicrob Agents. 2019 Nov;54(5):592-600. doi: 10.1016/j.ijantimicag.2019.08.001. Epub 2019 Aug 5.