MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)

Study Overview
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Brief Summary
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This is a randomized prospective study into metabolic adverse events during different types of initial antiretroviral therapy in HIV-1-infected men.

Detailed Description
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This is a randomized prospective study into metabolic adverse events during initial antiretroviral therapy in HIV-1-infected men. The following regimens are compared: lopinavir-ritonavir + Combivir and lopinavir-ritonavir + nevirapine (nucleoside reverse transcriptase inhibitor [NRTI]-sparing). Prior to the start of therapy and 3, 12, 24, and 36 months thereafter the distribution of body fat and bone density (bioelectrical impedance analysis [BIA], computed tomography [CT] and dual energy x-ray absorptiometry [DEXA]), lipid spectrum, mitochondrial DNA (peripheral blood mononuclear cells [PBMCs] and adipose tissue biopsies) and vascular measurements are performed. In addition, insulin sensitivity is measured in a subgroup of sixteen individuals by using a hyperinsulinemic euglycemic clamp and performing microvascular measurements. The aim of the study is to obtain prospective insight into the occurrence of various aspects of metabolic adverse events on the one hand and to compare an NRTI-containing therapy with an NRTI-sparing therapy on the other hand. The hypothesis is that in the NRTI-sparing arm, less metabolic and vascular changes are observed than in the NRTI containing regimen.

Official Title
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MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)

Conditions
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HIV Infections, HIV-Associated Lipodystrophy Syndrome

Intervention / Treatment
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* Drug: Lopinavir/ritonavir + zidovudine + lamivudine
* Drug: Lopinavir/ritonavir + nevirapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age between 18 and 70 years. No prior use of antiretroviral therapy Indication for antiretroviral treatment according to common standards Exclusion Criteria: Female sex Body mass index (kg/m2) > 35. Known history of diabetes mellitus or hyperlipidemia Use of coenzyme A reductase inhibitor or fibric acid derivative in the last 6 weeks before inclusion Use of the following medication: systemic corticosteroids, thiazide diuretics, calcium-entry blockers, angiotensin-converting inhibitors, nitrates Use of nandrolone or testosterone Any disorder or condition which can be expected to lead to lessened compliance with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lopinavir/ritonavir + zidovudine + lamivudine|nan|
|Drug: Lopinavir/ritonavir + nevirapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin resistance (3, 12, 24, 36 months) |  |  | 
| microvascular function (3, 12, 24, 36 months) |  |  | 
| lipid profile (3, 12, 24, 36 months) |  |  | 
| body composition (3, 12, 24, 36 months) |  |  | 
| macrovascular function (12, 24, 36 months) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mitochondrial DNA in PBMC and fatty tissue (12, 24, 36 months) |  |  | 
| gene expression, markers of mitochondrial toxicity, inflammation, apoptosis, fat cell differentiation in fatty tissue (12, 24, 36 months) |  |  | 
| bone mineral density (12, 24, 36 months) |  |  | 
| natural killer cells (3, 12, 24 months) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HIV-associated lipodystrophy syndrome