multi interventional study exploring hiv-1 residual replication: a step towards hiv-1 eradication and sterilizing cure

Conditions: Chronic Infection; HIV

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 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.

Keywords: dendritic cell vaccination using antiretroviral intensification auranofin histone deacetylase inhibitor residual viral replication hiv sanctuaries hiv latency