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

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: DRV/r; Drug: ATV/r

• Registration Number: NCT00756730
• Lead Sponsor: Community Research Initiative of New England

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2008-09-18
• Study First Submitted QC: 2008-09-19
• Study First Posted: 2008-09-22
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Results First Submitted: 2012-02-21
• Results First Submitted QC: 2012-06-08
• Results First Posted: 2012-07-13
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-18
• Last Update Posted: 2017-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

Read More

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:

  1. Pre-existing diabetes mellitus with asymptomatic, nonfasting glucose grade 3 elevations
  2. 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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Switch to DRV/r (800mg/100mg) QD	DRV/r	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.
Switch to ATV/r (300mg/100mg QD)	ATV/r	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

Primary Outcome Measures

Name	Time	Method
Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24.	baseline, 24 weeks	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.
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

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

Trial Locations

Locations (11)

Community Research Initiative; 🇺🇸 Boston, Massachusetts, United States

Abbott Northwestern Infectious Disease and Travel Clinic; 🇺🇸 Minneapolis, Minnesota, United States

Nicholaos C. Bellos, MD, PA; 🇺🇸 Dallas, Texas, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States

David M. Lee, M.D., P.A., a/b/a Uptown Physicians Group; 🇺🇸 Dallas, Texas, United States

Spectrum Medical Group; 🇺🇸 Phoenix, Arizona, United States

Community Research Initiative - West; 🇺🇸 Springfield, Massachusetts, United States

Philadelphia Fight; 🇺🇸 Philadelphia, Pennsylvania, United States

AIDS Community Health Center; 🇺🇸 Rochester, New York, United States

AIDS Healthcare Foundation; 🇺🇸 Los Angeles, California, United States