Raltegravir And Darunavir Antiretroviral in Antiretroviral Naive Patients
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00677300
- Lead Sponsor
- Dallas VA Medical Center
- Brief Summary
The purpose of this study is to determine whether a combination of raltegravir and darunavir is as effective as standard regimens in the treatment of HIV-infected patients who have not previously used antiretroviral drug (treatment naive)
- Detailed Description
STUDY RATIONALE:
The current guidelines for HIV treatment in antiretroviral naive patients recommend the use of two drugs in the nucleoside reverse transcriptase inhibitor (NRTI) class in addition to one drug in the protease inhibitor (PI) or in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class.
NRTI use is associated with significant toxicity, including mitochondrial dysfunction (mostly attributed to thymidine-analogue NRTIs): lipoatrophy, peripheral neuropathy, pancreatitis, lactic acidosis. There's also a significant risk of hypersensitivity reaction from Abacavir, and caution is needed when using Tenofovir in patients with renal failure.
Finding effective NRTI-free regimens would have a number of potential benefits including: 1) a significant expansion of therapeutic options; despite the growing number of antiretrovirals, treatment options might still be significantly limited in a patient with a number of baseline NRTI mutations or poor NRTI tolerance; 2) potential avoidance of toxicities.
Raltegravir is a leading candidate in a new class of antiretroviral medications called integrase inhibitors. It is currently approved for use in antiretroviral treatment experienced patients, but has been shown to have excellent virologic efficacy in naïve as well as heavily treatment experienced patients. It also has been shown to have unusually rapid virologic response. This profile might be excellent in delaying emergence of viral resistance in naïve patients.
Three phase III trials of Raltegravir in treatment experienced patients have been conducted (BENCHMRK trials). In both of these studies, more than 75 percent of patients receiving Raltegravir plus optimized background therapy (OBT) achieved viral load (HIV RNA) reductions to less than 400 copies/mL compared to more than 40 percent of patients receiving placebo plus OBT. Both studies also showed that Raltegravir plus OBT was generally well tolerated.
Darunavir is currently approved for use in HAART-experienced patients at the dose of 600 mg bid with ritonavir boosting. In subgroup analysis of the BENCHMRK trials, use of Raltegravir and Darunavir was associated with 90% virologic responses (HIV RNA \< 400 copies/mL) at 24 weeks in treatment experienced subjects. Also, the recently presented ARTEMIS study found once-daily Darunavir to be non-inferior to either once- or twice-daily lopinavir/ritonavir in antiretroviral naïve patients. After 48 weeks a time-to-loss-of-virologic response analysis determined that 84% assigned to darunavir and 78% assigned to lopinavir had a viral load below 50 copies. In subgroup analysis, DRV/r QD was superior to LPV/r (overall) in patients with baseline viral load ≥100,000 copies/mL Furthermore, the DRV/r QD group experienced a lower incidence of lipid abnormalities than the lopinavir/ritonavir group.
HYPOTHESES
We hypothesize that the virologic efficacy (time to loss of virologic response) at 48 weeks will be at least as high following a regimen of Raltegravir + boosted Darunavir as with a regimen of Tenofovir + Emtricitabine + boosted Darunavir.
We further hypothesize that a regimen of Raltegravir + boosted Darunavir will not result in higher rates of adverse events at 48 weeks than a regimen of Tenofovir + Emtricitabine + boosted Darunavir.
STUDY DESIGN AND DURATION
This is a randomized, active Control, safety/efficacy study. All eligible patients (antiretroviral naïve,) will be randomized (1:1) into two treatment groups:
1. Group A: will receive Raltegravir + Ritonavir-boosted Darunavir
2. Group B: will receive Tenofovir + Emtricitabine + Ritonavir-boosted Darunavir
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 85
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B Tenofovir/Emtricitabine Will receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Group A Darunavir Will receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Group A Raltegravir Will receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Group A Ritonavir Will receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Group B Darunavir Will receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Group B Ritonavir Will receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily)
- Primary Outcome Measures
Name Time Method Time from randomization to virologic failure (HIV viral load of 1,000 copies/ml or greater at or after Week 16 and before Week 24, or two consecutive HIV viral load of 50 copies/ml or greater at or after Week 24) Week 24
- Secondary Outcome Measures
Name Time Method Median change in CD4 count from baseline 48 Weeks Changes from baseline in insulin resistance measured by homeostasis model assessment (HOMA-IR) 48 weeks Percentage of patients with treatment-emergent fasting hypertriglyceridemia (TG >400) or hypercholesterolemia (TC >240) 48 weeks Median change in limb fat from baseline, by DEXA scan 48 weeks
Trial Locations
- Locations (2)
Dallas VA Medical Center
🇺🇸Dallas, Texas, United States
Parkland Health & Hospital System
🇺🇸Dallas, Texas, United States