D4T or Abacavir Plus Vitamin Enhancement in HIV-Infected Patients (DAVE)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Acidosis, Lactic

Intervention / Treatment
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* Drug: d4T
* Drug: Abacavir
* Drug: Riboflavin and Thiamine (Supplementation)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: d4T|See Detailed Description.|
|Drug: Abacavir|See Detailed Description.|
|Drug: Riboflavin and Thiamine (Supplementation)|See Detailed Description.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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.) |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decline of RVLA levels |  |  | 
| Absolute level of change of RVLA levels using baseline values as a covariant |  |  | 
| Proportion of patients improving/normalizing exercise testing mitochondrial dysfunction pattern |  |  | 
| Time to event: time to normalize venous lactic acid |  |  | 
| Time to event: premature therapy discontinuation, viral load rebound, and progression to a new AIDS defining illness or death |  |  | 
| 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 |  | 16 weeks | 
| Change in absolute CD4 from baseline |  |  | 
| Absolute CD4/CD8 counts |  |  | 
| Incidence of grade III and greater adverse drug effects |  |  | 
| Metabolic laboratory assessments (anion gap, lipid and hepatic profile, and hematology) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elevated Lactic Acid