Efficacy Study of Substitution of Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Controlled Trial to Evaluate the Efficacy of Substituting Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors in Individuals With Virologic Suppression for at Least 12 Weeks

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Darunavir (DRV/r)
* Drug: continue on current dual boosted PI


Participation Criteria
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Eligibility Criteria
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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: Use a double barrier method to prevent pregnancy (i.e., using a condom with either a diaphragm or cervical cap) Or Use hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or Use an intra uterine device (IUD) in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or Be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile).

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 |
| --- | --- |
| Active Comparator: Switch to DRV/r<br>Switch to DRV/r at a dose of 600/100 BID for 48 weeks | Drug: Darunavir (DRV/r)<br>* Switch to DRV/r at a dose of 600/100 BID for 48 weeks<br>|
| Active Comparator: Continue on Current Dual Boosted PI<br>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 are followed for an additional 24 weeks | Drug: continue on current dual boosted PI<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 48 weeks | 
| 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. | baseline and 24 weeks | 
| 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. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV/AIDS, darunavir, Protease inhibitors, Dual boosted, Treatment experienced