Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r

Study Overview
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Brief Summary
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For participants with HIV taking either lopinavir or fosamprenavir who have elevated triglycerides, this trial will study the change in triglycerides after switching protease inhibitors.

Detailed Description
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This Phase IV trial will look at lipid and virologic responses after a switch to a more lipid-friendly antiretroviral regimen. Participants will be randomized to receive either boosted atazanavir or boosted darunavir given once daily, along with background NRTIs. This 24-week study will require 4 visits after randomization for evaluation, monitoring, and lab studies.

Official Title
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Randomized, Open-label Study of Switch From Lopinavir/Ritonavir (LPV/r) or Fosamprenavir/Ritonavir (FPV/r) to Either Once Daily Atazanavir/Ritonavir (ATV/r) or Once Daily Darunavir/Ritonavir (DRV/r) (Plus Background Nucleoside Reverse Transcriptase Inhibitors) in Patients Experiencing Triglyceride Elevations While Receiving LPV/r or FPV/r.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: ATV/r
* Drug: DRV/r


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently receiving Antiretroviral Therapy (ART) regimen including LPV/r or FPV/r and > or equal to 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Patient must be on a stable regimen containing LPV/r or FPV/r for at least 12 weeks prior to screening. Documentation of an undetectable Human Immunodeficiency Virus (HIV) viral load (VL<400 copies/ml) using an FDA approved assay for a minimum of twelve weeks prior to screening AND undetectable HIV viral load using an FDA approved ultrasensitive assay at screening. No evidence of HIV protease resistance as defined by the Stanford HIV database Currently receiving first protease inhibitor unless switch to LPV/r or FPV/r was for non-virologic reasons Fasting triglycerides > 200 mg/dL No ongoing issues that in the opinion of the investigator would lead to decreased ability to comply with the study procedures If currently receiving a proton pump inhibitor, the dose is < omeprazole 20 mg or the equivalent dose of another proton pump inhibitor If patient is receiving another lipid lowering medication, it must be at a stable dose Exclusion Criteria: Currently receiving an ART regimen other than > or equal to two NRTIs and either LPV/r or FPV/r Prior use of darunavir or atazanavir CDC Class C Illness diagnosed within 30 days of screening Patient is currently receiving the following Hydroxamethylglutaryl-coA (HMGCoA) reductase inhibitor medications (statins): pravastatin, lovastatin, simvastatin Patient is currently receiving a bile acid sequestrant (cholestyramine, colestipol, and colesevelam) Grade 3 or 4 Laboratory abnormalities as defined by a standardized grading scheme based on the DAIDS table with the following exceptions: Pre-existing diabetes mellitus with asymptomatic, nonfasting glucose grade 3 elevations Subjects with asymptomatic grade 3 fasting triglyceride or cholesterol elevations Clinical or laboratory evidence of clinically significant liver impairment/dysfunction disease or cirrhosis Note: Individuals co-infected with chronic hepatitis B or C viruses will be allowed to enter the trial if their condition is clinically stable and they will not require therapy during the course of the study. Individuals diagnosed with acute viral hepatitis at screening will not be allowed to enroll during acute phase Active substance abuse or significant psychiatric illness that in the opinion of the investigator might interfere with study compliance Use of any investigational agents 30 days prior to screening Life expectancy < 6 months in the opinion of the investigator Pregnancy or breast feeding Female subject of childbearing potential (i.e., heterosexually active, and not surgically sterile or at least two years post-menopausal) not using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Switch to DRV/r (800mg/100mg) QD<br>We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. For this arm the sbject switched to DRV/r at a dose 800mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study. | Drug: DRV/r<br>* We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. Switch to DRV/r at a dose 800mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.<br>|
| Other: Switch to ATV/r (300mg/100mg QD)<br>We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. For this are the subject switched to ATV/r at a dose of 300mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study | Drug: ATV/r<br>* Switch to ATV/r at a dose of 300mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.<br>* Other names: Atazanavir/r;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. | A 10% decline in triglycerides (TGs) was determined to be clinically significant. The percentage of people that experienced a 10% decline was calculated by dividing the number who had a decline of 10% TGs by the total number of participants in the arm. | baseline, 24 weeks | 
| At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL |  | 24 weeks | 
| The Change in Fasting Triglyceride Level From Baseline to Week 24 |  | Baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 |  | Week 4, 12 & 24 | 
| Difference in CD4 From Baseline to Week 24 |  | baseline to Week 24 | 
| Total Cholesterol in the Two Study Groups at 24 Weeks |  | Week 24 | 
| LDL Cholesterol at Week 24 |  | week 24 | 
| HDL Cholesterol at Week 24 |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lopinavir, ritonavir, atazanavir, fosamprenavir, darunavir, anti-retroviral, AIDS, HIV, LARD, triglyceride, protease inhibitors, treatment Experienced