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Sponsors and Collaborators: |
National Institute of Allergy and Infectious Diseases (NIAID) Adult AIDS Clinical Trials Group University of North Carolina Merck and Company Abbott |
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Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00576290 |
Valproic acid (VPA) is an antiseizure drug, but data suggest that it may allow anti-HIV drugs access to resting HIV. A reduction in resting HIV would mean better control of the disease. The purpose of this study is to determine if the addition of VPA and raltegravir to a successful anti-HIV drug regimen will reduce the amount of resting HIV.
Condition | Intervention | Phase |
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HIV Infections |
Drug: Valproic Acid Drug: raltegravir |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study |
Official Title: | MK-0518 Intensification and HDAC Inhibition in Depletion of Resting CD4+ T Cell HIV Infection |
Estimated Enrollment: | 8 |
Study Start Date: | September 2009 |
Estimated Study Completion Date: | September 2010 |
Estimated Primary Completion Date: | September 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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2A
Early study discontinuation for participants who have not responded to raltegravir and valproic acid in Step 1
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Drug: Valproic Acid
oral medication initially dosed at 1000 to 2000 mg daily and escalated weekly until a plasma level of 50 to 100 ug/ml has been reached
Drug: raltegravir
Oral HDAC inhibitor initially dosed at 1000 to 2000 mg daily, then escalated weekly to as much as 60 mg/kg/day until a plasma level of 50 to 100 mcg/ml has been reached
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2B: Experimental
Continuation of raltegravir and current HAART regimen after treatment with valproic acid for those who responded to raltegravir and valproic acid in Step 1
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Drug: Valproic Acid
oral medication initially dosed at 1000 to 2000 mg daily and escalated weekly until a plasma level of 50 to 100 ug/ml has been reached
Drug: raltegravir
Oral HDAC inhibitor initially dosed at 1000 to 2000 mg daily, then escalated weekly to as much as 60 mg/kg/day until a plasma level of 50 to 100 mcg/ml has been reached
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When HIV has just been made, it enters a CD4 cell's nucleus. An enzyme in the nucleus called integrase helps HIV hide in the cell's own DNA, and another enzyme called histone deacetylase (HDAC) helps it stay hidden. While HIV is hiding in the DNA, it is not active and cannot be targeted by currently available highly active antiretroviral therapy (HAART). VPA, a drug used to treat seizures, is an HDAC inhibitor, and raltegravir is a newly FDA-approved integrase inhibitor. Taking VPA and raltegravir may prevent HIV from being able to hide in CD4 cells, allowing HAART to eliminate HIV that would normally be hidden. The purpose of this study is to determine whether adding raltegravir and VPAto the participant's current HAART regimen will reduce the number of resting HIV in CD4 cells.
This study will last at least 24 weeks. In Step 1, participants will continue on their current HAART regimen, as determined by their own doctor, and begin taking raltegravir daily. At Week 8, participants will begin taking valproic acid daily. Participants will start at a low dose of valproic acid, and the dose will escalate weekly until appropriate levels are reached, as determined by blood test. Study visits for Step 1 will occur at screening, study entry, and Weeks 1, 2, 4, 8, 9, 10, 12, 16, 20, and 24. At these visits, physical exams and urine and blood collection will occur. At some visits, genital secretion collection will occur. Leukapheresis to determine resting HIV levels will occur at Weeks 4, 8, 20, and 24. Participants will not receive HAART through this study.
Step 2 will begin at Week 24; all participants will stop taking valproic acid at the start of this step. If they have not responded to the raltegravir and valproic acid given in Step 1, they will enter Step 2A and discontinue the study. Participants who have responded to raltegravir and valproic acid will continue take raltegravir and their current HAART regimen until Week 40. Leukapheresis to determine resting HIV level will occur at Weeks 36 and 40. A final follow-up visit will occur by Week 48. Other study visits will occur at Weeks 30, 36, and 40. At these visits, physical exams and urine and blood collection will occur. At some visits, genital secretion collection will occur.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: David M. Margolis, MD | 919-966-6638 | dmargo@med.unc.edu |
United States, North Carolina | |
University of North Carolina Memorial Hospital | |
Chapel Hill, North Carolina, United States |
Principal Investigator: | David M. Margolis, MD | The University of North Carolina, Chapel Hill |
Principal Investigator: | Joseph Eron, MD | The University of North Carolina, Chapel Hill |
Responsible Party: | DAIDS ( Rona Siskind ) |
Study ID Numbers: | U01AI125868, CID 0704, R01 A164074, R01 AI45297, U01 A125868 |
Study First Received: | December 17, 2007 |
Last Updated: | September 24, 2008 |
ClinicalTrials.gov Identifier: | NCT00576290 |
Health Authority: | United States: Federal Government |
Treatment Experienced Histone deacetylase Histone remodeling |
Virus Diseases Sexually Transmitted Diseases, Viral HIV Infections Sexually Transmitted Diseases |
Acquired Immunodeficiency Syndrome Valproic Acid Retroviridae Infections Immunologic Deficiency Syndromes |
Communicable Diseases Neurotransmitter Agents RNA Virus Infections Slow Virus Diseases Tranquilizing Agents Molecular Mechanisms of Pharmacological Action Immune System Diseases Physiological Effects of Drugs Psychotropic Drugs Central Nervous System Depressants |
Enzyme Inhibitors Infection Antimanic Agents Pharmacologic Actions Therapeutic Uses Lentivirus Infections GABA Agents Central Nervous System Agents Anticonvulsants |