NCT00677300

Raltegravir And Darunavir Antiretroviral in Antiretroviral Naive Patients

Evaluation of Safety and Efficacy of Raltegravir/Darunavir Combination in Antiretroviral-Naive Patients

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 85 (actual)
• Sponsor: Dallas VA Medical Center · Federal
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	Raltegravir	400mg P.O. (orally) twice daily for 48 weeks
DRUG	Darunavir	800 mg P.O. (orally) once daily
DRUG	Ritonavir	100mg once daily
DRUG	Tenofovir/Emtricitabine	300 mg/200 mg P.O. (orally) once daily

Timeline

• Start date: 2009-01-01
• Primary completion: 2012-10-01
• Completion: 2012-12-01
• First posted: 2008-05-14
• Last updated: 2014-09-08

Locations

2 sites across 1 country: United States