This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Efficacy of VHM After Treatment Interruption in Subjects Initiating ART During Acute HIV Infection

This study has been completed.
Sponsor:
Collaborators:
The Thai Red Cross AIDS Research Centre
Cooper Human Systems
Information provided by (Responsible Party):
Prof.Praphan Phanuphak, MD, PhD, South East Asia Research Collaboration with Hawaii
ClinicalTrials.gov Identifier:
NCT02475915
First received: June 3, 2015
Last updated: March 29, 2016
Last verified: March 2016
  Purpose

This study is a two-arm prospective 1:1 randomised controlled trial comparing the proportion of patients between:

Group 1: vorinostat/hydroxychloroquine/maraviroc (VHM) co-administered with anti-retroviral therapy (ART) Group 2: ART only who are able to maintain HIV RNA < 50 copies/ml following treatment interruption. Subjects will be recruited from RV254/SEARCH 010, an acute HIV infection cohort conducted by the Thai Red Cross AIDS Research Centre in Bangkok, Thailand. The study will run for a minimum of 34 weeks from screening.


Condition Intervention Phase
Acute HIV Infection Drug: Vorinostat Drug: Hydroxychloroquine Drug: Maraviroc Drug: Tenofovir Drug: Emtricitabine Drug: Efavirenz Drug: Darunavir Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study to Compare the Efficacy of Vorinostat/Hydroxychloroquine/Maraviroc (VHM) in Controlling HIV After Treatment Interruption in Subjects Who Initiated ART During Acute HIV Infection

Resource links provided by NLM:


Further study details as provided by Prof.Praphan Phanuphak, MD, PhD, South East Asia Research Collaboration with Hawaii:

Primary Outcome Measures:
  • Proportion of patients with HIV RNA < 50 copies/ml following ART interruption [ Time Frame: 24 weeks ]

Secondary Outcome Measures:
  • Time to HIV RNA rebound after treatment interruption between VHM +ART versus ART only arms defined as > 1000 HIV-1 RNA copies/ml on two consecutive plasma samples [ Time Frame: 24 weeks ]
  • To compare the cell-associated spliced HIV RNA in total CD4+ T cells between the VHM+ ART and ART only arms. Measured as copies multi-spliced RNA/1000000 cells [ Time Frame: 34 weeks ]
    HIV expression

  • To compare the cell-associated unspliced HIV RNA in total CD4+ T cells between the VHM+ ART and ART only arms. Measured as copies unspliced RNA/1000000 18S [ Time Frame: 34 weeks ]
    HIV expression

  • To compare markers of HIV persistence measured as total, integrated and 2-LTR circles HIV DNA. Measured as DNA copies/1000000 cells [ Time Frame: 34 weeks ]
    HIV persistence

  • To compare histone acetylation between the VHM + ART and ART only groups Expressed as mean fluorescence intensity [ Time Frame: 10 weeks ]
    Serious Adverse Events

  • To compare adverse events both related and unrelated to the combination of hydroxychloroquine and maraviroc between arms graded according to NCI Common Terminology for Adverse Events [ Time Frame: 34 weeks ]
    Serious Adverse Events

  • The occurrence and severity of acute retroviral syndrome between arms following treatment interruption using a combination of at least 3 clinical symptoms such as fever, lymphadenopathy and pharyngitis [ Time Frame: 34 weeks ]
    Acute Retroviral Syndrome


Enrollment: 15
Study Start Date: January 2015
Study Completion Date: March 2016
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ART + VHM

Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.

Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.

Drug: Vorinostat
Vorinostat (suberoylanilide hydroxamic acid) inhibits histone deacetylases class I and II. Vorinostat is supplied as 100mg capsules and will be administered at 400mg/ day in 2 week cycles beginning at week 0 for 10 weeks - 42 doses.
Other Name: Zolinza
Drug: Hydroxychloroquine
Hydroxychloroquine is supplied as 200mg tablets and will be administered at week 0 for 10 weeks
Other Name: Plaquenil
Drug: Maraviroc
Maraviroc will be administered at 150 to 600mg/ml twice daily depending on the subject's ART regimen at week 0 for 10 weeks
Other Name: Selzentry
Drug: Tenofovir
NRTI. Tenofovir will be administered at 300mg 1 X day at week 0 for 10 weeks
Other Name: Viread
Drug: Emtricitabine
NRTI. Emtricitabine will be administered at 200mg 1 X day at week 0 for 10 weeks
Other Name: Emtriva
Drug: Efavirenz
NNRTI. Efavirenz will be administered at 600 mg 1 X day at week 0 for 10 weeks
Other Name: Sustiva
Drug: Darunavir
Protease Inhibitor. Darunavir will be administered at a dose of 900mg 1 X day for subjects on NNRTI based ART beginning at week 8 until week 10
Other Name: Prezista
Active Comparator: ART alone
Group 2: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and either an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Drug: Tenofovir
NRTI. Tenofovir will be administered at 300mg 1 X day at week 0 for 10 weeks
Other Name: Viread
Drug: Emtricitabine
NRTI. Emtricitabine will be administered at 200mg 1 X day at week 0 for 10 weeks
Other Name: Emtriva
Drug: Efavirenz
NNRTI. Efavirenz will be administered at 600 mg 1 X day at week 0 for 10 weeks
Other Name: Sustiva
Drug: Darunavir
Protease Inhibitor. Darunavir will be administered at a dose of 900mg 1 X day for subjects on NNRTI based ART beginning at week 8 until week 10
Other Name: Prezista

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected adults 18-60 years
  • Initiated ART during acute HIV infection period, defined serologically as up to a positive but incomplete profile by Western blot and has been on ART for at least 42 weeks
  • HIV RNA <50 copies/ml within the past 7 months (28 weeks)
  • CD4 cell count ≥ 450 cells/μl on at least 2 occasions during the past 6 months
  • Informed consent

Exclusion Criteria:

  • Any significant medical illness in the past 12 weeks
  • Any evidence of AIDS-defining opportunistic infection
  • Current or gastrointestinal disease that may impact absorption of the study drug
  • ALT or AST >3X upper limit of normal
  • Hemoglobin, white blood cell counts or platelets ≥ grade 2 by US NIH DAIDS grading system
  • History of diabetes or fasting glucose >126mg/dl
  • Documented hepatitis B infection as indicated by the presence of HBsAG
  • History of clinically significant cardiac disease or clinically significant EKG abnormalities
  • History of retinal disease
  • History of malignancy
  • Females who are pregnant or with a positive urine pregnancy test during screening or women of child bearing potential who are unwilling to use an acceptable method of contraception to avoid pregnancy for 4 weeks before, during the study and 4 weeks after the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02475915

Locations
Thailand
SEARCH, the Thai Red Cross AIDS Research Centre
Bangkok, Thailand, 10330
Sponsors and Collaborators
South East Asia Research Collaboration with Hawaii
The Thai Red Cross AIDS Research Centre
Cooper Human Systems
Investigators
Principal Investigator: Praphan - Phanuphak, MD, PhD The Thai Red Cross AIDS Research Centre
  More Information

Publications:

Responsible Party: Prof.Praphan Phanuphak, MD, PhD, South East Asia Research Collaboration with Hawaii
ClinicalTrials.gov Identifier: NCT02475915     History of Changes
Other Study ID Numbers: SEARCH 019
Study First Received: June 3, 2015
Last Updated: March 29, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Prof.Praphan Phanuphak, MD, PhD, South East Asia Research Collaboration with Hawaii:
Treatment interruption
Controlling HIV

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Efavirenz
Emtricitabine
Darunavir
Maraviroc
Hydroxychloroquine
Vorinostat
HIV Protease Inhibitors
Protease Inhibitors
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 26, 2017