The purpose of this study is to determine the best way to treat people on d4T 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 d4Twithout vitamin supplements;
• Group 3 will switch from d4T to abacavir and receive the vitamins;
• Group 4 will switch from d4T to abacavir without vitamins 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

Condition	Intervention	Phase
Elevated Lactic Acid	Drug: d4T (drug); Abacavir (drug) ; Riboflavin and Thiamine (Supplementation)	Phase II Phase III

Further Study Details: 

Primary Outcomes: 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.
Secondary Outcomes: - Rate pf decline pf 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 or below to 50 copies/mL during the 16 week follow-up period on an intention to treat basis; - 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)
Expected Total Enrollment:  80

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Be HIV-positive
• Be 18 years of age or more
• Have a viral load equal 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 Co-enzyme 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 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00143702

Sophie Geeraerts      604-806-8758    sophie@hivnet.ubc.ca

Canada, British Columbia
      St. Paul''''s Hospital, Vancouver,  British Columbia,  V6Z 1Y6,  Canada; Recruiting
Canada, Ontario
      Positive Care Clinic, Toronto,  Ontario,  Canada; Recruiting

Study chairs or principal investigators

Julio Montaner, MD,  Principal Investigator,  University of British Columbia   

Study ID Numbers:  P00-0159; CTN 169
Last Updated:  September 1, 2005
Record first received:  August 31, 2005
ClinicalTrials.gov Identifier:  NCT00143702
Health Authority: Canada: Health Canada
ClinicalTrials.gov processed this record on 2005-09-06