Official Title: “Randomized, Open-Label Study of Continued Stavudine Versus Abacavir Substitution With or Without Riboflavin and Thiamine Supplementation in HIV-Infected Patients Who Have Elevated Venous Lactic Acid While on Stavudine-Based Therapy (DAVE)”

The purpose of this study is to determine the best way to treat people on d4T (stavudine) with high levels of lactic acid. Switching from d4T to abacavir will be assessed. Adding riboflavin and thiamine will also be assessed.

Participants will be randomly assigned to one of four groups: - Group 1 participants will continue to take d4T as part of their antiretroviral (ARV) regimen, and will be given the vitamin supplements - Group 2 will continue to take d4T without vitamin supplements - Group 3 will switch from d4T to abacavir and receive the vitamins - Group 4 will switch from d4T to abacavir without vitamin supplements.

The study plans to involve eighty participants from Canada and Argentina for a treatment period of 16 weeks and a follow-up visit at week 24.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment

Study Primary Completion Date: August 2006

Intervention(s) in this Clinical Trial

• Drug: d4T
  • See Detailed Description.
• Drug: Abacavir
  • See Detailed Description.
• Drug: Riboflavin and Thiamine (Supplementation)
  • See Detailed Description.

Primary Measures

• Proportion of patients per arm with random venous lactic acid (RVLA) below or equal to 2.1 mmol/L* at 16 weeks. (* Confirmed by a second determination 7-14 days later.)
  • Time Frame: 16 weeks
    Safety Issue?: No

Secondary Measures

• Rate of decline of RVLA levels
  • Time Frame: Unspecified
    Safety Issue?: No
• Absolute level of change of RVLA levels using baseline values as a covariant
  • Time Frame: Unspecified
    Safety Issue?: No
• Proportion of patients improving/normalizing exercise testing mitochondrial dysfunction pattern
  • Time Frame: Unspecified
    Safety Issue?: No
• Time to event: time to normalize venous lactic acid
  • Time Frame: Unspecified
    Safety Issue?: No
• Time to event: premature therapy discontinuation, viral load rebound, and progression to a new AIDS defining illness or death
  • Time Frame: Unspecified
    Safety Issue?: No
• Proportion of patients with at least three consecutive HIV-1 RNA determinations equal to or below 50 copies/mL during the 16 week follow-up period on an intention to treat basis
  • Time Frame: 16 weeks
    Safety Issue?: No
• Change in absolute CD4 from baseline
  • Time Frame: Unspecified
    Safety Issue?: No
• Absolute CD4/CD8 counts
  • Time Frame: Unspecified
    Safety Issue?: No
• Incidence of grade III and greater adverse drug effects
  • Time Frame: Unspecified
    Safety Issue?: No
• Metabolic laboratory assessments (anion gap, lipid and hepatic profile, and hematology)
  • Time Frame: Unspecified
    Safety Issue?: No

Inclusion Criteria:

• Be HIV-positive
• Be 18 years of age or older
• Have a viral load equal to or below 50 copies/mL
• Have been on a d4T-containing multiple drug regimen (at least three agents in total) for at least six months
• Have been on a stable ARV regimen for the three months prior to enrollment
• Have a venous lactic acid measurement above 2.1 mmol/L within the three months prior to enrollment and two consecutive measurements above 2.1 but lower than 6.0 within a two-week period of screening
• Be willing to discontinue L-carnitine and/or coenzyme Q10
• Be willing and able to provide informed consent

Exclusion Criteria:

• Pregnancy or breastfeeding
• Venous lactic acid equal to or above 6.0 mmol/L
• Previous exposure to abacavir
• Virologic rebound while on a previous regimen consisting of dual or triple nucleoside reverse transcriptase inhibitors (NRTIs)
• Use of hydroxyurea within the three months prior to enrollment
• Use of metformin
• Any acute cardiopulmonary illness or infection
• New AIDS-defining illness diagnosed within four weeks of enrollment
• Riboflavin or thiamine supplementation above 20 mg/day within 30 days prior to enrollment

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of British Columbia

Overall Clinical Trial Officials and Contacts

Julio Montaner, MD Principal Investigator University of British Columbia  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00143702

Study ID Number: P00-0159

ClinicalTrials.gov Identifier: NCT00143702

Health Authority: Canada: Health Canada