 |
|
|
| |
The Impact of Maraviroc on Insulin Sensitivity, Lipids and
Adipokines after 2 weeks in HIV Negative Male Volunteers
|
| |
| |
Reported by Jules Levin
EACS Cologne, Nov 11-14 2009
P. Randell, A. Jackson, S. Mandalia J. Taylor, G. Moyle
CHELSEA AND WESTMINSTER HOSPITAL, DEPARTMENT OF HIV & GENITOURINARY MEDICINE, LONDON, UNITED KINGDOM
AUTHOR CONCLUSIONS
In HIV negative male subjects, 2 weeks of dosing with Maraviroc 300mg twice daily does not have a significant impact on insulin sensitivity, adipokines (adiponectin and leptin) or lipid parameters.
BACKGROUND
Certain antiretrovirals are associated with metabolic side effects including body fat changes, hypercholesterolaemia and insulin resistance1.
The hyperinsulinaemic euglycaemic clamp2 is considered the gold standard for investigating insulin sensitivity in a research setting. The development of insulin resistance has been demonstrated in healthy volunteers after dosing with stavudine3, ritonavir4, lopinavir/ritonavir5 but not with tenofovir6, amprenavir4 or atazanavir5.
The impact of the newer drug classes on insulin sensitivity has been less extensively investigated. Raltegravir given for 2 weeks did not significantly impact insulin sensitivity in healthy volunteers7. The impact of CCR5 inhibitors on insulin sensitivity has not previously been evaluated.
OBJECTIVE
To investigate the impact of Maraviroc on insulin sensitivity and lipids in HIV negative male volunteers.
METHODS
A randomised, placebo controlled, two period crossover study design was utilised.
Important Eligibility Criteria:
- BMI<28 kg/m2
- Waist:hip ratio<0.97
- Absence of any medication or disease process likely to cause marked disturbances on lipid and glucose homeostasis.
- Fasting serum glucose, cholesterol and triglycerides within normal limits.
Sixteen healthy male volunteers were randomised (1:1) to receive Maraviroc 300mg twice daily for two weeks followed by two weeks of matching placebo or took placebo initially followed by Maraviroc.
Insulin sensitivity (M/I) by hyperinsulinaemic, euglycaemic clamp and assessment of fasting lipid parameters was performed at baseline and at completion of each treatment period.
RESULTS
One subject did not have a clamp performed after 2 weeks of placebo.
There was no significant period effect and no statistically significant change from baseline or between groups in insulin sensitivity or lipids. Intra-individual changes in M/I are presented below:
A significant period effect was observed with triglycerides and the changes in triglycerides by treatment order are shown below:
Mean percentage (SD) changes in lipid parameters for the Maraviroc vs placebo treatment periods were: 1.16 (9.46)% vs 0.13 (10.56)% for total cholesterol; -0.56 (12.92)% vs 1.54 (18.4)% for LDL cholesterol and 0.94 (14.64)% vs -1.96 (7.10) for HDL cholesterol.
Adiponectin and leptin levels were not significantly altered in either arm during the study.
REFERENCES
1. Grinspoon S, Carr A. Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults. N Engl J Med. 2005;352:48-62.
2. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214-E23.
3. Fleischman A, Johnsen S, Systrom DM, et al. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab. 2007;292:E1666-E73.
4. Lee GA, Rao M, Mulligan K, et al. Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. AIDS. 2007;21(16):2183-90.
5. Noor MA, Parker RA, O'Mara E, et al. The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. AIDS. 2004;18(16):2137-44.
6. Randell P, Jackson A, Zhong L, Yale K & Moyle G. The Impact of Tenofovir on Insulin Sensitivity and Lipids in Healthy Volunteers. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy 2008.
7. Randell P, Jackson A, Mandalia S, Taylor J & Moyle G. The impact of raltegravir and lopinavir/ritonavir on lipids, adiponectin and peripheral glucose disposal in HIV negative subjects. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention 2009.
|
| |
|
|
|
|
|
