HIV Infection And Metabolic Abnormalities Protocol 1 (HAMA001)

Study Overview
=================
Brief Summary
-----------------
This is a prospective, non-randomised, 48 week study of the effect of protease inhibitor (PI) containing and non-PI containing antiretroviral regimens on the expression of adipocyte specific genes, protein levels and cellular structure in HIV-infected individuals, naive to therapy, who are starting therapy for the first time.

Detailed Description
-----------------
Antiretroviral medications, used to treat HIV infection, cause side effects. These include changes in composition of fat throughout the body (loss in some areas and accumulation in others), elevations in blood lipids and abnormalities in glucose metabolism. The resulting syndrome is known as HIV associated lipodystrophy or HIVLD. In HIV negative populations, such abnormalities in lipid and glucose metabolism are associated with an increased risk of developing cardiovascular disease (CVD). The aim of this study is to characterize the changes that occur in body composition and metabolism with antiretroviral treatment and compare them to changes in fat tissue structure and function and surrogate markers for cardiovascular disease.

Official Title
-----------------
Analysis of Lipodystrophy in HIV-Infected Individuals A Prospective, Non-randomised, 48 Week Study of the Effect of PI Containing and Non-PI Containing Antiretroviral Regimens on the Expression of Adipocyte Specific Genes, Protein Levels and Cellular Structure in HIV-infected Individuals, Naive to Therapy, Who Are Starting Therapy for the First Time

Conditions
-----------------
HIV-Associated Lipodystrophy Syndrome, Cardiovascular Disease

Intervention / Treatment
-----------------
* Drug: Lamivudine
* Drug: Stavudine
* Drug: Didanosine
* Drug: Zidovudine
* Drug: Tenofovir
* Drug: Abacavir
* Drug: Efavirenz (EFV)
* Drug: Nevirapine
* Drug: Indinavir
* Drug: Saquinavir
* Drug: Amprenavir
* Drug: Ritonavir
* Drug: Nelfinavir
* Drug: Tipranavir
* Drug: enfuvirtide (T20)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >18. Be able to provide written consent to perform in the trial. HIV antibody positive at time of entry to the study. Specific to HIV Infection and Metabolic Abnormalities Protocol 1 (HAMA) part A only: Be naive to antiretroviral medication. Specific to HAMA part B only: Have had a minimum total exposure to antiretroviral medications (to include drugs from more than one drug class) of 48 weeks at time of recruitment. Have had a minimum of 48 weeks interval since completion of HAMA part A. Exclusion Criteria: Any history of, or ongoing, mental or physical condition (including suspected or known diagnosis of ischaemic heart disease), which, in the opinion of the investigator, would impede the subject's ability to participate in the trial. Prior use of growth hormone or glucocorticoid or anabolic steroid products within the previous six months. Prior use of supraphysiological doses of testosterone or oestrogen replacement therapy within the previous year. Alcohol or substance abuse which in the opinion of the investigator would affect the patients ability to participate in the trial. Prior use of any retinoid-containing compound within the previous six months. Abnormal coagulation. Previous allergic reaction or known allergy to local anaesthetic. Previous or concomitant use of medications, which, in the opinion of the investigator, would affect the subject's ability to participate in all activities involved in the trial. Any grade-three laboratory abnormality recorded from screening bloods, which, in the opinion of the investigator, would impede the subject's ability to safely complete all study requirements. Any finding on screening clinical examination, which, in the opinion of the investigator, would impede the subject's ability to participate in the rest of the trial. Pregnancy Specific to HAMA part A only: Prior use of anti-retroviral agents (including protease inhibitors, nucleoside or non-nucleoside reverse transcriptase inhibitors, investigational antiretroviral agents or fusion inhibitors). Entry of individuals who have had previous antiretroviral therapy as part of post exposure prophylaxis will be at the discretion of the study investigators.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lamivudine|nan|
|Drug: Stavudine|nan|
|Drug: Didanosine|nan|
|Drug: Zidovudine|nan|
|Drug: Tenofovir|nan|
|Drug: Abacavir|nan|
|Drug: Efavirenz (EFV)|nan|
|Drug: Nevirapine|nan|
|Drug: Indinavir|nan|
|Drug: Saquinavir|nan|
|Drug: Amprenavir|nan|
|Drug: Ritonavir|nan|
|Drug: Nelfinavir|nan|
|Drug: Tipranavir|nan|
|Drug: enfuvirtide (T20)|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate changes in adipocyte structure and function in HIV-infected individuals treated with antiretroviral therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate changes in adipocyte function with changes in body composition and metabolic parameters in individuals beginning their first antiretroviral regimen |  |  | 
| To examine changes in adipocyte function in HIV-infected volunteers both prior to and after initiation of treatment in order to determine changes arising directly as a result of therapy |  |  | 
| To investigate changes in adipocyte function in pre-treated HIV-infected volunteers with and without established signs of HIVLD in order to determine if changes in function correlate with particular phenotypes such as lipoatrophy or buffalo hump |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Metabolic abnormality, Lipodystrophy, Cardiovascular disease, Treatment Naive, Treatment Experienced, HIV Infections