Evaluation of a Dose Reduction of Darunavir (400 mg/d) in Virologically Suppressed HIV-1 Patients (DARULIGHT)

Phase II Trial Assessing the Efficacy of a Reduced Dose Strategy of Darunavir to 400 mg/d in HIV-1 Infected Patients Virologically Suppressed Under a Once Daily Regimen Including Darunavir 800 mg/d and Two Nucleoside Reverse Transcriptase Inhibitors (NRTI), to Maintain the Viral Load Lower Than 50 Copies / mL at 48 Weeks of Treatment

Phase II trial assessing the efficacy of a reduced dose strategy of darunavir to 400 mg/d in HIV-1 infected patients virologically suppressed under a once daily regimen including darunavir 800 mg/d and two nucleoside reverse transcriptase inhibitors (NRTI), to maintain the viral load lower than 50 copies / mL at 48 weeks of treatment.

Study Overview

• Status: Completed
• Conditions: HIV INFECTION
• Intervention / Treatment: Drug: Darunavir

Detailed Description

Principal objective: To evaluate the proportion of subjects virologically suppressed at week 48 (viral load=VL ≤ 50 cp/mL) under a tri-therapy containing the darunavir at the dose of 400 mg/d.

Secondary objectives: To evaluate between baseline and week 48: proportions of subjects: in virological failure (confirmed VL > 50 cp/mL) confirmed by a 2nd measure made between 2 to 4 weeks, with VL ≤ 50 cp/mL and between 20 and 50 cp/mL, emerging drug resistance if virological failure, CD4 cell count evolution, HIV DNA evolution, morphological and glucido-lipid parameters modifications, digestive treatment tolerance , adherence to treatment, overall cost of antiretroviral therapy, factors associated to virological failure including baseline and nadir CD4 cell count, darunavir plasma level, baseline HIV DNA viral load.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hôpital Saint Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infected adults,
• age ≥ 18 years,
• with a once-a-day ritonavir-boosted darunavir 800mg/j containing regimen plus 2 NRTI (≥ 6 months),
• virologically controlled (VL ≤ 50 cp/ml,
• ≥ 1 year,
• at least 2 VL spaced at least 3 months apart in the last 12 months) CD4 count ≥ 300/mm3 ≥ 6 months,
• virus sensible to darunavir and the used NRTI (pretreatment resistance genotypic test available) and
• with no history of virological failure (VL > 200 cp/mL after ≥ 6 months under PI and/or used NRTI),
• no current opportunistic infection,
• renal clearance ≥ 60 mL/min if tenofovir is used,
• transaminases (SGOT, SGPT) plasma levels < 2N,
• hemoglobin > 11 g/dL,
• platelets count > 150 000/mm3,
• negative pregnancy test in women with childbearing potential,
• informed written consent signed by both the investigator and the subject,
• national insurance scheme (article L1121-11 of the French Public Health code),
• no participation to any other clinical trial

Exclusion Criteria:

• HIV-2 infection,
• current antiretroviral therapy different from a once-a-day ritonavir-boosted darunavir 800mg/j containing regimen plus 2 NRTI,
• virus genotypically resistant to darunavir and the used NRTIs,
• history of virological failure (VL > 200 cp/mL after ≥ 6 months under PI and/or used NRTI),
• irregular follow-up and/or history of lack of adherence to ART ≤ 12 months,
• current pregnancy,
• current opportunistic infection,
• associated treatment containing one or more drugs interacting with hepatic cytochromes,
• any addictive behaviors (alcohol consumption, drugs …) likely to jeopardize the safety of the treatment and / or patient compliance and adherence to the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darunavir 400mg/d; Tri-therapy containing Darunavir at dose of 400 mg/d.	Drug: Darunavir; to assess efficacy of a reduced dose strategy of darunavir to 400 mg/d in HIV-1 infected patients virologically suppressed under a once daily regimen including darunavir 800 mg/d and two nucleoside reverse transcriptase inhibitors (NRTI), to maintain the viral load lower than 50 copies / mL at 48 weeks of treatment.; Other Names: Prezista

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with therapeutic success, defined as no virological failure	Virological failure is defined as confirmed VL > 50 cp/mL and no change of the strategy	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportions of patients with virological failure (confirmed VL > 50 cp/ml)	Week 48
Proportions of patients with VL < 50 cp/ml	Week 12, Week 24, Week 36, Week 48
Proportions of patients with VL between 20 and 50 cp/ml	Week 12, Week 24, Week 36, Week 48
Change from baseline in blood CD4 cell count at week 12, week 24, week 36 and week 48	Week 12, Week 24, Week 36, Week 48
Change from baseline in blood HIV DNA at week 48	Week 48
Emerging drug resistance if virological failure	Week 48
Treatment adherence	Week 48
Change from baseline in blood lipids at week 24 and week 48	Week 24 and Week 48
Change from baseline in glucose at week 24 and week 48	Week 24 and Week 48
Treatment Digestive tolerance	Week 48

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases

Publications and helpful links

General Publications

• Le MP, Chaix ML, Chevret S, Bertrand J, Raffi F, Gallien S, El Abbassi EMB, Katlama C, Delobel P, Yazdanpanah Y, Saillard J, Molina JM, Peytavin G; ANRS 165 DARULIGHT Study Group. Pharmacokinetic modelling of darunavir/ritonavir dose reduction (800/100 to 400/100 mg once daily) in a darunavir/ritonavir-containing regimen in virologically suppressed HIV-infected patients: ANRS 165 DARULIGHT sub-study. J Antimicrob Chemother. 2018 Aug 1;73(8):2120-2128. doi: 10.1093/jac/dky193.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: February 23, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 10, 2015

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Darunavir
• Other Study ID Numbers: ANRS 165 DARULIGHT