HIV Infections
Conditions
Keywords
lopinavir, ritonavir, atazanavir, fosamprenavir, darunavir, anti-retroviral, AIDS, HIV, LARD, triglyceride, protease inhibitors, treatment Experienced
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.
Interventions
DRUGATV/r
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.
DRUGDRV/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. 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.
Sponsors
Tibotec Pharmaceutical Limited
Community Research Initiative of New England
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| LDL Cholesterol at Week 24 | week 24 |
| Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 4, 12 & 24 |
| HDL Cholesterol at Week 24 | 24 weeks |
| Difference in CD4 From Baseline to Week 24 | baseline to Week 24 |
| Total Cholesterol in the Two Study Groups at 24 Weeks | Week 24 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to DRV/r, 800mg/100mg QD | 25 |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD Virologically suppressed patients on a regimen containing Lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) were switched to ATV/r | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | discontinued due to rash prior to week 4 | 0 | 1 |
| Overall Study | persistent low-level viremmia | 0 | 1 |
Baseline characteristics
| Characteristic | Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Total | Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD |
|---|---|---|---|
| Age, Customized | 48 years | 47 years | 46 years |
| Baseline antiretroviral medications - Protease inhibitors fosamprenavir/ritonavir (FPV/r) | 2 participants | 3 participants | 1 participants |
| Baseline antiretroviral medications - Protease inhibitors Lopinavir/ritonavir (LPV/r) | 23 participants | 46 participants | 23 participants |
| Baseline medications - Nucleoside analogs other | 5 Participants | 7 Participants | 2 Participants |
| Baseline medications - Nucleoside analogs viread (TDF)/emtriva (FTC) | 15 Participants | 32 Participants | 17 Participants |
| Baseline medications - Nucleoside analogs ziagen (ABC)/Epivir (3TC) | 5 Participants | 10 Participants | 5 Participants |
| CD4 Count | 584 cells/mm3 | 569 cells/mm3 | 554 cells/mm3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 19 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 29 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Lipid Lowering Medications fibrate | 5 participants | 11 participants | 6 participants |
| Lipid Lowering Medications fish oil | 5 participants | 8 participants | 3 participants |
| Lipid Lowering Medications niacin | 0 participants | 1 participants | 1 participants |
| Lipid Lowering Medications none | 9 participants | 20 participants | 11 participants |
| Lipid Lowering Medications statin | 6 participants | 9 participants | 3 participants |
| Region of Enrollment United States | 25 participants | 49 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 23 Participants | 45 Participants | 22 Participants |
| Viral Load | NA copies/mL | 0 copies/mL | NA copies/mL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 25 | 8 / 24 |
| serious Total, serious adverse events | 1 / 25 | 1 / 24 |
Outcome results
Primary
At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL
Time frame: 24 weeks
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL | 48 percentage of participants |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL | 55 percentage of participants |
Primary
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.
Time frame: baseline, 24 weeks
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia. Neither subject met criteria for virologic failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. | 80 percentage of patients |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. | 73 percentage of patients |
Primary
The Change in Fasting Triglyceride Level From Baseline to Week 24
Time frame: Baseline to week 24
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | The Change in Fasting Triglyceride Level From Baseline to Week 24 | -126 mg/dL |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | The Change in Fasting Triglyceride Level From Baseline to Week 24 | -88 mg/dL |
Secondary
Difference in CD4 From Baseline to Week 24
Time frame: baseline to Week 24
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Difference in CD4 From Baseline to Week 24 | 10.75 cells/mm^3 | Standard Error 17.67 |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | Difference in CD4 From Baseline to Week 24 | 14.28 cells/mm^3 | Standard Error 19.77 |
Secondary
HDL Cholesterol at Week 24
Time frame: 24 weeks
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | HDL Cholesterol at Week 24 | 38 mg/dL |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | HDL Cholesterol at Week 24 | 40 mg/dL |
Secondary
LDL Cholesterol at Week 24
Time frame: week 24
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | LDL Cholesterol at Week 24 | 116 mg/dL |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | LDL Cholesterol at Week 24 | 111 mg/dL |
Secondary
Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24
Time frame: Week 4, 12 & 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 4 | 100 percentage of participants |
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 12 | 100 percentage of participants |
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 24 | 100 percentage of participants |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 4 | 100 percentage of participants |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 12 | 100 percentage of participants |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 | Week 24 | 100 percentage of participants |
Secondary
Total Cholesterol in the Two Study Groups at 24 Weeks
Time frame: Week 24
Population: Two patients in the ATV/r arm discontinued prior to week 24: 1 due to a grade 2 rash, and one due to low level viremia.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Switch to Darunavir/Ritonavir (DRV/r) , 800mg/100mg QD | Total Cholesterol in the Two Study Groups at 24 Weeks | 195 mg/dL |
| Switch to Atazanavir/Ritonavir (ATV/r), 300mg/100mg QD | Total Cholesterol in the Two Study Groups at 24 Weeks | 195 mg/dL |