Post-prandial Lipid Effects of Raltegravir (RAL) vs Ritonavir -Boosted Darunavir (DRV-r) in Anti-retroviral Therapy (ART)- Naive Adults or Adults Recommencing ART.

Study Overview
=================
Brief Summary
-----------------
This is a research study into the effects of three drugs used to treat HIV infection. Some drugs used to treat HIV have been associated with changes in blood fats such as cholesterol that could be harmful over the long-term, because these blood fat changes have been associated with a small, increased risk of heart disease and stroke in some studies of adults with HIV. Now that HIV can be controlled for long periods in most patients, and because heart disease is one of the biggest causes of illness and death in the general population, it is important to develop new HIV treatments that control HIV effectively but do not cause abnormal blood fats. Hypothesis: That Raltegravir will result in less post-prandial lipid disturbances than ritonavir-boosted darunavir.

Official Title
-----------------
Post-prandial Lipid Effects of Raltegravir (RAL) vs Ritonavir-boosted Darunavir (DRV-r) in Anti-retroviral Therapy (ART)-Naive Adults or Adults Recommencing ART.

Conditions
-----------------
HIV, Cardiovascular Disease

Intervention / Treatment
-----------------
* Drug: raltegravir plus truvada
* Drug: Darunavir, ritonavir, tenofovir/emtricitabine (Truvada)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed, informed consent Age >18 years HIV infection documented by HIV antibody test and Western Blot prior to study entry No previous ART OR no ART for 6 months prior to randomisation CD4+ count of <500 cells/mm or viral load >10,000 copies/ml within 60 days prior to randomisation No genotypic resistance to Raltegravir, Tenofovir/emtricitabine, Darunavir, Ritonavir Body mass index less than 30kg/m2 Exclusion Criteria: Primary HIV infection within the last 6 months Active infection or opportunistic illness within the previous 30 days Use of any medication contra-indicated with ritonavir-boosted darunavir or raltegravir Use of lipid-lowering therapy Diabetes mellitus (fasting glucose >7.0mml/l or a prior diagnosis of diabetes) Use of oral prednisolone > 7.5mg daily or equivalent pregnancy or Breast feeding proven hypersensitivity to one or more components of the study meal

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1.Raltegravir plus truvada<br>Raltegravir 400mg twice daily plus truvada 300mg/200mg once daily for 24 weeks | Drug: Darunavir, ritonavir, tenofovir/emtricitabine (Truvada)<br>* Darunavir two 400mg tablets with one ritonavir 100mg capsule once daily plus Tenofovir/emtricitabine (Truvada) one 300mg/200mg tablet once daily with food for 24 weeks<br>* Other names: Tenofovir/emtricitabine;|
| Active Comparator: 2. ritonavir boosted darunavir plus truvada<br>Darunavir 800mg with ritonavir 100mg plus truvada 300mg/200mg once daily for 24 weeks | Drug: raltegravir plus truvada<br>* raltegravir 400 mg tablet with truvada 300/200 mg tablet for 24 weeks<br>* Other names: Isentress;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the effects of ritonavir plus darunavir daily to raltegravir twice daily on post prandial lipid responses over 24 weeks | Fasting samples will be taken for total cholesterol, LDL and HDL cholesterol, and triglycerides. Repeat lipid samples will be collected before a high fat meal is consumed. After the meal is completed , blood will be collected at 1, 2, 3, and 4 hours at baseline, week 4 and week 24 visits. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety | Safety parameters will be assessed by measurement of urea and electrolytes, LFTs, urine protein to creatinine ratio | 24 weeks | 
| Other metabolic parameters | Fasting metabolic parameters will be assessed. Study staff and participants will be blinded to the results fo these tests until completion of the study or parameters become sginificantly abnormal | 24 weeks | 
| Arterial stiffness |  | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, cardiovascular disease, post prandial lipids, ritonavir, darunavir, raltegravir, arterial stiffness, tonometry