Lactate Metabolism Study in HIV Infected Persons

2014-08-26 22:49:41 | BioPortfolio


Lactic acidosis is a potentially life-threatening disease associated with the treatment of chronic HIV infection. Although acidosis is rare, hyperlactatemia is common and may have long term consequences yet to be recognized. Lactic acidosis is a manifestation of mitochondrial toxicity; consequences which have yet to be fully recognized and understood. In this study, we propose to look at lactate clearance and production by two methods, in four treatment groups, including HIV positive subjects on highly active antiretroviral therapy (HAART) treatment regimes and without HAART regimes, with liver steatosis and without, and compared with HIV negative controls. Supplementation with cofactors thiamine, niacin and L-carnitine, which may have a positive effect on lactate metabolism by facilitating mitochondrial function, will be studied as well.


The management of chronic HIV infection is increasingly dependent upon the management of long term toxicities of therapy. Toxicities are often metabolic and include hyperlipidemia, hyperglycemia, osteopenia and lipodystrophy. While more rare, lactic acidosis may present also, and is associated with mortality. The consequences of chronic hyperlactatemia are not well understood, but it is known that the cause is likely related to mitochondrial toxicity of nucleoside analogues, which are the cornerstone class of HIV therapies.

No treatments for the syndrome of chronic lactic acidosis have been proven, but evidence exists which suggests that the utilization of cofactors such as thiamine, riboflavin and L-carnitine in the management of the acute syndrome; these factors may alleviate the mitochondrial compromise.

The mechanism underlying lactic acidemia may be a result of both increased production (as a result of mitochondrial dysfunction), and poor clearance of lactate by the liver which is the primary organ for clearance. Some of this liver dysfunction could also be attributable to mitochondrial toxicity.

In this study we propose to study lactate metabolism among persons with chronic HIV infection (both on treatment and treatment naive) and compare the results to uninfected control population. We will also study a subset of HIV infected persons with known underlying liver disease. Two methodologies will be used: a lactate challenge test and a forearm ischemia test. The effect of supplementation with cofactors which may have a positive effect on lactate metabolism by facilitating mitochondrial function will be studied as well. All persons enrolled for evaluation will have these tests repeated 4-6 weeks after supplementation with standardized doses of cofactors thiamine and L-carnitine between tests. Fat tissue samples and PBMC's will be collected and analyzed for quantity and function, and participants will have liver ultrasounds. Liver biopsies will be completed on those subjects where clinically indicated. The results of the study will provide important insights into the effects on lactate metabolism, nucleoside analogues, and HIV itself.

Our primary hypothesis is that persons on D4T/ddI/ddC/AZT containing highly active antiretroviral therapy (HAART) will demonstrate increased lactate production compared to HIV negative controls; that lactate metabolism will be normalized after treatment with cofactors (riboflavin, thiamine, L-carnitine); that persons with liver disease on therapy will demonstrate prolonged lactate clearance; and that persons changed to a non-D4T/ddI/ddC/AZT containing regime will demonstrate a decrease in lactate production from baseline.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Health Services Research


HIV Infections


cofactor supplementation (thiamine, riboflavin, L-carnitine)


Queen's University
K7L 3N6


Active, not recruiting


Queen's University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-26T22:49:41-0400

Clinical Trials [461 Associated Clinical Trials listed on BioPortfolio]

Thiamine Supplementation in Heart Failure Patients Receiving Full Medical Therapy

The study is performed to consider the effect of thiamine supplementation on symptoms and signs of patients with heart failure and systolic and diastolic function of left ventricle.

D4T or Abacavir Plus Vitamin Enhancement in HIV-Infected Patients (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 riboflavi...

Carnitine Levels and Carnitine Supplementation in Type I Diabetes

The purpose of this study is to determine whether type I diabetics with carnitine deficiency exhibit increased numbers of hypoglycemic (low blood sugars) events and if unrecognized hypogl...

The Effect of Riboflavin in Crohn's Disease

This study will evaluate if suppelementation of the diet with riboflavin in Crohn's disease patients will result in an increase in the amount of F. prausnitzii.

Thiamine Supplementation to Improve Cardiac Function in Patients With Congestive Heart Failure

Working Hypothesis: a treatment with thiamine improves functional status and heart function of patients with congestive heart failure when on a diuretic treatment.

PubMed Articles [4594 Associated PubMed Articles listed on BioPortfolio]

Characterization of thiamine uptake and utilization in Candida spp. subjected to oxidative stress.

Candida species are associated with an increasing number of life-threatening infections (candidiases), mainly due to the high resistance of these yeast-like fungi to antifungal drugs and oxidative str...

The Effect of Two-Week L-Carnitine Supplementation on Exercise -Induced Oxidative Stress and Muscle Damage.

This study was conducted to assess the effect of Two-week L-carnitine supplementation on known markers of oxidative stress and muscle damage following acute bouts of exercise in active healthy young m...

Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up.

Systemic primary carnitine deficiency is an autosomal recessive disorder caused by the deficiency of carnitine transporter. Main features are cardiomyopathy, myopathy and hypoglycemic encephalopathy. ...

Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency.

We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due...

L-carnitine supplementation reduces short-term neutrophil-lymphocyte ratio in patients undergoing coronary artery bypass grafting.

We aimed to investigate whether L-carnitine supplementation effects the neutrophil/lymphocyte ratio in patients undergoing coronary artery bypass grafting.

Medical and Biotech [MESH] Definitions

An enzyme that hydrolyzes thiamine pyrophosphate to thiamine monophosphate plus inorganic phosphate. EC 3.6.1.-.

A thiamine antagonist due to its inhibition of thiamine pyrophosphorylation. It is used to produce thiamine deficiency.

An enzyme that catalyzes the formation of O-acetylcarnitine from acetyl-CoA plus carnitine. EC

An enzyme that catalyzes the formation of riboflavin from two molecules of 6,7-dimethyl-8-ribityllumazine, utilizing a four-carbon fragment from one molecule which is transferred to the second molecule. EC

A dietary deficiency of riboflavin causing a syndrome chiefly marked by cheilitis, angular stomatitis, glossitis associated with a purplish red or magenta-colored tongue that may show fissures, corneal vascularization, dyssebacia, and anemia. (Dorland, 27th ed)

More From BioPortfolio on "Lactate Metabolism Study in HIV Infected Persons"


Relevant Topics

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

AIDS; Acquired Immune Deficiency Syndrome. HIV; Human Immunodeficiency Virus HIV infection causes AIDS. HIV infection also causes the production of anti-HIV antibodies, which forms the test for HIV in patients. People who have the HIV antibodies are ...

Searches Linking to this Trial