HIV Infections
Conditions
Keywords
HIV/AIDS, darunavir, Protease inhibitors, Dual boosted, Treatment experienced
Brief summary
This study will evaluate patients who have achieved virologic suppression (\< 400 copies/mL) on any dual protease inhibitor (PI) combination, to determine whether patients can substitute both PIs with the single boosted PI darunavir given 600/100 ritonavir (RTV) twice daily (BID) and maintain comparable virologic suppression (% \< 50 c/mL) for 24 weeks.
Detailed description
The purpose of this study is to determine if patients who have achieved virologic suppression (\< 400 copies/mL) on any dual PI combination, can substitute both PIs with the single boosted PI darunavir given 600/100 rtv bid and maintain comparable virologic suppression (% \< 50 c/mL) for 24 weeks. Randomized, non-blinded, multicenter, 48 week, controlled trial to assess the non-inferiority of substituting DRV/r for a dual boosted PI combination in patients with stable virologic suppression on a regimen containing a dual boosted PI combination plus at least one additional FDA-licensed antiretroviral agent from another class. Participants will be randomized (1:1) to one of the included treatment arms.
Interventions
DRUGDarunavir (DRV/r)
Switch to DRV/r at a dose of 600/100 BID for 48 weeks
DRUGcontinue on current dual boosted PI
Continue on current dual boosted PI until week 24. At week 24, participants will be allowed to cross over to the DRV/r arm provided that they have maintained virologic suppression (\< 400 copies/ml) for the first 24-weeks of the study and be followed for an additional 24 weeks
Sponsors
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
* Age 18 years or older * Treatment with a stable antiretroviral regimen containing two protease inhibitors, one additional FDA-licensed agent from another class (except NNRTIs) and a boosting dosage of ritonavir (100 BID or QD) for at least 12 weeks prior to screening * No plans to make any changes in HIV treatment regimen (other than those required by study) in the next 48 weeks. * HIV-1 RNA \< 400 copies/ml based on the most recent value done as part of routine care at least 12 weeks prior to screening; and \< 400 at screening * Any CD4 count is allowed * Written informed consent to participate
Exclusion criteria
* Current regimen includes an NNRTI * CDC Class C Illness diagnosed within 30 days of screening * Lab abnormalities as defined by a standardized grading scheme based on the DAIDS table * Any grade 3 or 4 toxicity with the following exceptions: * Pre-existing diabetes with glucose elevations ≥ grade 3 * triglyceride or total cholesterol elevations ≥ grade 3 * Clinical or laboratory evidence of clinically significant liver impairment/dysfunction, disease or cirrhosis Note: Individuals co-infected with chronic hepatitis B or C will be allowed to enter the trial if their condition is clinically stable. 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 * Prior use of darunavir or known allergy to any of the components of darunavir * Breast feeding * Female subject of childbearing potential 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. Note: Hormonal based contraception may not be reliable when taking darunavir, therefore to be eligible for this study, women of childbearing potential who may have vaginal intercourse should either: 1. Use a double barrier method to prevent pregnancy (i.e., using a condom with either a diaphragm or cervical cap) Or 2. Use hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or 3. Use an intra uterine device (IUD) in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or 4. Be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Successful Virologic Suppression | 24 weeks | Amount of HIV RNA copies per ml blood collected from subjects as measured by the Ultra-sensitive HIV-1 PCR (Roche Cobas). Successful virologic suppression is defined as \< 50 copies/ml blood. The result is the percentage of participants with successful virologic suppression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Economic Impact of a Substitution of Dual Boosted PIs With DRV/r | 48 weeks | To assess the economic impact of DRV/r substitution for dual boosted PIs, we compared the average wholesale acquisition costs for the drugs in US Dollars ($) per month. The wholesale acquisition cost in US dollars ($) for each ART regimen was determined and the difference between the cost for the experimental and control groups was calculated and reported as US dollar savings per month. |
| Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | baseline and 24 weeks | We collected fasting total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides from all participants in both arms of the study. We calculated the differences between the values at week 24 and baseline for the participants in both arms. We reported the mean of the change from baseline to week 24. |
| Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | 24 weeks | Participants in the experimental arm completed treatment satisfaction questionnaires at 24 weeks, and the control arm at 48 weeks (24 weeks after mid-study crossover to boosted darunavir). The questionnaires used numeric satisfaction scales (+3 much more satisfied now to -3 much less satisfied now). We reported the median and ranges for each question for each study arm. |
Countries
United States
Participant flow
Recruitment details
Five multicenter sites were used these included medical and research clinics.
Participants by arm
| Arm | Count |
|---|---|
| Switch to DRV/r Switch to DRV/r at a dose of 600/100 BID for 48 weeks | 12 |
| Continue on Current Dual Boosted PI This is the control group. Subjects in this arm stay on their current regimen - a dual boosted PI combination. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Continue on Current Dual Boosted PI | Switch to DRV/r | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Continuous | 51 years | 46 years | 50 years |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 3 / 12 |
Outcome results
Primary
The Percentage of Participants With Successful Virologic Suppression
Amount of HIV RNA copies per ml blood collected from subjects as measured by the Ultra-sensitive HIV-1 PCR (Roche Cobas). Successful virologic suppression is defined as \< 50 copies/ml blood. The result is the percentage of participants with successful virologic suppression.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch to DRV/r | The Percentage of Participants With Successful Virologic Suppression | 100 Percentage of Participants |
| Continue on Current Dual Boosted PI | The Percentage of Participants With Successful Virologic Suppression | 100 Percentage of Participants |
Secondary
Economic Impact of a Substitution of Dual Boosted PIs With DRV/r
To assess the economic impact of DRV/r substitution for dual boosted PIs, we compared the average wholesale acquisition costs for the drugs in US Dollars ($) per month. The wholesale acquisition cost in US dollars ($) for each ART regimen was determined and the difference between the cost for the experimental and control groups was calculated and reported as US dollar savings per month.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch to DRV/r | Economic Impact of a Substitution of Dual Boosted PIs With DRV/r | 217 US dollars savings per month |
| Continue on Current Dual Boosted PI | Economic Impact of a Substitution of Dual Boosted PIs With DRV/r | 0 US dollars savings per month |
Secondary
Lipid Fraction Results, Mean of the Change From Baseline to Week 24.
We collected fasting total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides from all participants in both arms of the study. We calculated the differences between the values at week 24 and baseline for the participants in both arms. We reported the mean of the change from baseline to week 24.
Time frame: baseline and 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Switch to DRV/r | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in Total Cholesterol | -6 mg/dL |
| Switch to DRV/r | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in HDL-Cholesterol | -1 mg/dL |
| Switch to DRV/r | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in LDL-Cholesterol | -4 mg/dL |
| Switch to DRV/r | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in Triglycerides | -13 mg/dL |
| Continue on Current Dual Boosted PI | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in LDL-Cholesterol | 2 mg/dL |
| Continue on Current Dual Boosted PI | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in Total Cholesterol | 2 mg/dL |
| Continue on Current Dual Boosted PI | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in Triglycerides | 0 mg/dL |
| Continue on Current Dual Boosted PI | Lipid Fraction Results, Mean of the Change From Baseline to Week 24. | Change in HDL-Cholesterol | 1 mg/dL |
Secondary
Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now)
Participants in the experimental arm completed treatment satisfaction questionnaires at 24 weeks, and the control arm at 48 weeks (24 weeks after mid-study crossover to boosted darunavir). The questionnaires used numeric satisfaction scales (+3 much more satisfied now to -3 much less satisfied now). We reported the median and ranges for each question for each study arm.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Switch to DRV/r | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How satisfied are your with your current treatment | 3 Units on a Scale (+3 to -3) |
| Switch to DRV/r | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How satisfied are you with any side-effects | 2 Units on a Scale (+3 to -3) |
| Switch to DRV/r | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How convenient is your treatment | 3 Units on a Scale (+3 to -3) |
| Switch to DRV/r | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How well does your treatment fit your lifestyle | 3 Units on a Scale (+3 to -3) |
| Switch to DRV/r | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | Would you recommend your treatment to someone else | 3 Units on a Scale (+3 to -3) |
| Switch to DRV/r | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How likely are you to continue your treatment | 3 Units on a Scale (+3 to -3) |
| Continue on Current Dual Boosted PI | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | Would you recommend your treatment to someone else | 2.5 Units on a Scale (+3 to -3) |
| Continue on Current Dual Boosted PI | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How satisfied are your with your current treatment | 2.5 Units on a Scale (+3 to -3) |
| Continue on Current Dual Boosted PI | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How well does your treatment fit your lifestyle | 3 Units on a Scale (+3 to -3) |
| Continue on Current Dual Boosted PI | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How satisfied are you with any side-effects | 2.5 Units on a Scale (+3 to -3) |
| Continue on Current Dual Boosted PI | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How likely are you to continue your treatment | 2.5 Units on a Scale (+3 to -3) |
| Continue on Current Dual Boosted PI | Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) | How convenient is your treatment | 3 Units on a Scale (+3 to -3) |