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

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; HIV
• Intervention / Treatment: Drug: Darunavir, ritonavir, tenofovir/emtricitabine (Truvada); Drug: raltegravir plus truvada

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
    • Sydney, New South Wales, Australia, 2010
      • St Vincent Hospital, Clinical Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1.Raltegravir plus truvada; Raltegravir 400mg twice daily plus truvada 300mg/200mg once daily for 24 weeks	Drug: Darunavir, ritonavir, tenofovir/emtricitabine (Truvada); 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; Other Names: Prezista; Norvir; Tenofovir/emtricitabine
Active Comparator: 2. ritonavir boosted darunavir plus truvada; Darunavir 800mg with ritonavir 100mg plus truvada 300mg/200mg once daily for 24 weeks	Drug: raltegravir plus truvada; raltegravir 400 mg tablet with truvada 300/200 mg tablet for 24 weeks; Other Names: Isentress; tenofovir disoproxil fumarate

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

Collaborators and Investigators

• Sponsor: St Vincent's Hospital, Sydney
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Andrew D Carr, Professor, St Vincent's Hospital - Sydney, Australia

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: December 9, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (Estimate): December 13, 2010

Study Record Updates

• Last Update Posted (Estimate): January 12, 2015
• Last Update Submitted That Met QC Criteria: January 8, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: HIV; cardiovascular disease; raltegravir; post prandial lipids; ritonavir; darunavir; arterial stiffness; tonometry
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Darunavir
• Other Study ID Numbers: ROaR+

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No