MK-0518 Intensification And HDAC Inhibition In Depletion Of Resting CD4+ T Cell HIV Infection

NCT00614458 | Terminated Phase 2 Results DMC

• 4 other identifiers: 10493R01AI064074P30AI050410U01AI067854
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to see if HIV that persists despite current antiviral therapy can be targeted by new treatments. We will see if adding Raltegravir (MK-0518) and Valproic acid (VPA) to current ART can decrease the amount of latent HIV.

Conditions

HIV Infections

Keywords

latent HIV; resting CD4+ T cell; valproic acid (VPA); Raltegravir (MK-0518) intensification; HIV replication; treatment experienced

Outcome Measures

Primary Outcomes (1)

• A Change in the Number of HIV Infected Cells.

  A change in infected cells from prior to the initiation of VPA and MK0518 to after 20 weeks of treatment.

  20 weeks

Study Arms (1)

Raltegravir and VPA to ART

EXPERIMENTAL

raltegravir 400mg po BID; valproic acid 1000mg - 2000mg daily

Drug: Raltegravir; valproic acid

Interventions

Raltegravir; valproic acid DRUG

raltegravir 400mg po BID; valproic acid 1000mg - 2000mg daily

Also known as: raltegravir (MK 0518), Valproic acid (VPA) (depakote)

Raltegravir and VPA to ART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• Men and women age ≥18 years.
• Ability and willingness of subject or legal guardian/representative to give written informed consent.
• Karnofsky performance status \>70.
• Willing to adhere to protocol therapy and judged adherent to antiretroviral therapy, and can comply with time requirements for protocol-specified visits and evaluations.
• On potent antiretroviral therapy, defined as at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus at least 1 protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI), without changes in the 24 weeks immediately prior to entry. Prior changes in or elimination of medications for easier dosing schedule, intolerance, or toxicity are permitted.
• Have no contraindications to valproic acid (VPA) therapy (pregnancy, bleeding disorders, history of pancreatitis, history of hepatitis).
• Have adequate vascular access for leukopheresis
• Plasma HIV-1 RNA never \> 50 copies/ml on two consecutive occasions for ≥ 6 months.
• CD4 cell count \> 300 cells/µl.
• Screening serum fasting glucose below 120 mg/dl, creatinine no more than 1.5 times the upper limit of the normal range, serum AST, ALT, and total bilirubin less than 2 times the upper limit of the normal range, and fasting triglycerides \< 400mg/dl.
• Female study volunteers who are not of reproductive potential or whose male partner(s) has undergone successful vasectomy with documented azoospermia or has documented azoospermia for any other reason, are eligible without requiring the use of contraception.
• All women of reproductive potential must have a negative urine beta-HCG pregnancy test performed at screening, day 0, week 4, week 8, week 12, and every scheduled study visit thereafter.
• All study volunteers must agree not to participate in a conception process and, if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use two reliable methods of contraception simultaneously while receiving the protocol-specified medications and for 6 weeks after stopping the medications. Subjects must use a reliable barrier method of contraception along with another form of contraception. For women receiving ritonavir, estrogen-based contraceptives are not reliable and an alternative method should be used.

You may not qualify if:

• Receiving zidovudine (AZT). Due to the inhibition of zidovudine metabolism mediated by Valproic acid (VPA) a theoretical increase risk of zidovudine-induced anemia exists.
• Using drugs known to interact with valproate or raltegravir (MK-0518)
• Pregnant or nursing.
• Anemic (Hemoglobin \< 10gm/dl)
• Seropositive for hepatitis C RNA or hepatitis B surface antigen within 90 days prior to entry.
• Have signs or symptoms of hepatic decompensation
• Received blood transfusions or hematopoetic growth factors within 90 days.
• Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy, investigational agents, immunomodulators.
• Active drug or alcohol use or dependence.
• Serious illness requiring systemic treatment or hospitalization until subject either completes therapy or has been clinically stable on therapy, in the opinion of the site investigator, for at least 90 days prior to entry.
• Compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric illness or a physical illness, e.g., infectious disease.
• Treatment for an active AIDS-defining opportunistic infection within 90 days prior to screening.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Abbott: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, Eron J, Cohen M, Margolis DM. Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS One. 2010 Feb 23;5(2):e9390. doi: 10.1371/journal.pone.0009390.

  PMID: 20186346 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; Valproic Acid

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Professor of Medicine, Director Translational Research IGHID
• Organization: UNC Chapel Hill

dmargo@med.unc.edu

919 966 6388

Study Officials

• David M Margolis, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 13, 2008
• Study Start: April 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: October 25, 2011
• Results First Posted: October 25, 2011

Record last verified: 2011-09

Locations

US (1)