Effects of Melatonin on Metabolic Abnormalities in HIV Patients Treated with Antiretroviral Drugs

Abstract

Aims: Highly Active Antiretroviral Therapy (HAART) is the current care standard for treating patients with HIV/AIDS. Although HAART has is the only regimen potent enough to decrease viral load, adverse events may limit its efficacy. Metabolic disorders are common in patients treated with HAART. Melatonin (N-acetyl-5-methoxytryptamine) was initially thought to be exclusively of pineal origin but recent studies have shown that melatonin synthesis may occur in several cells and organs. Melatonin has been shown to have a variety of functions and research during the last decade has proven the indole to be a direct free radical scavenger and indirect antioxidant. Due to these activities and possibly others that remain to be defined, melatonin has been shown to reduce toxicity and increase the efficacy of a large number of drugs. This study evaluated the effects of melatonin supplementation (6mg / day / 30 days) in AIDS patients using antiretroviral therapy (HAART).
 Methodology: Current study was carried out in a double-blind, placebo-controlled and completely randomized design. AIDS patients who had metabolic alterations were selected. Patients were divided into two groups: Group I (HAART) consisted of patients receiving placebo once a day in the evening. Group II (HAART+ Melatonin) comprised patients who received the melatonin (6 mg) once a day in the evening for one month. Clinical and laboratorial evaluation was performed before and after 30 days. Clinical evaluation was performed to assess the patients´ overall clinical state. Patients were instructed to report any complications. Laboratorial evaluation was performed. Glucose levels were determined by glucose oxidase method and ELISA (Genway Biotechnology, USA), respectively, following manufacturer’s instructions. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were performed by the kinetic colorimetric method; triglycerides, total cholesterol and creatinine were performed by enzymatic colorimetric method, both provided by Gold Analisa Diagnóstica Ltda. 
 Results: Sixty patients who had some metabolic abnormalities (glucose levels above 100.0 mg/dL or total cholesterol above 200 mg/dL or triglycerides above 200 mg/dL) participated in the study. All had been using HAART therapy for at least five years, with an average 15-year infection period. Patient´s age ranged between 35 and 49 years, with a mean of 43.7 years. Fasting glucose was significantly lower in subjects in Group I treated with melatonin when compared with subjects included in the control group not treated with melatonin after one month of treatment. Levels of blood glucose were 23% lower in patients who used melatonin, with reference rates after one month of treatment. Current study revealed that 40% (12/30) of the patients had changes in AST liver enzymes (> 38 U/I), 30% (9/30) had changes in ALT levels (> 38 U/I) and 30% (9/30) had GGT levels (> 40 U/I). Results obtained after the use of melatonin suggest melatonin activity on the liver. Significant differences between groups in plasma cholesterol indicate that melatonin exerted better improvement of blood lipid composition. Melatonin would lower cholesterol in liver and decrease plasma cholesterol. Above all, melatonin could decrease oxidative stress and improve dyslipidemia.
 Conclusion: Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the efficacy of the drugs, its use may be important and significant as a combination therapy with HAART. Current study which investigated the effect of melatonin associated with antiretroviral treatment demonstrated beneficent effects on metabolic abnormalities in AIDS patients.