Acidosis, Lactic
Conditions
Keywords
Elevated Lactic Acid
Brief summary
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.
Interventions
DRUGd4T
See Detailed Description.
DRUGAbacavir
See Detailed Description.
DRUGRiboflavin and Thiamine (Supplementation)
See Detailed Description.
Sponsors
GlaxoSmithKline
CIHR Canadian HIV Trials Network
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 | — |
| Rate of decline of RVLA levels | — |
| 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) | — |
| 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 |
Countries
Canada
Outcome results
None listed