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

Phase 2

Completed

• Conditions: HIV INFECTION
• Interventions: Drug: Darunavir

• Registration Number: NCT02384967
• Lead Sponsor: ANRS, Emerging Infectious Diseases

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-02-23
• Study Start: 2015-03
• Study First Submitted QC: 2015-03-04
• Study First Posted: 2015-03-10
• Primary Completion: 2016-10
• Study Completion: 2016-10
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-23
• Last Update Posted: 2017-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Darunavir 400mg/d	Darunavir	Tri-therapy containing Darunavir at dose of 400 mg/d.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Proportions of patients with VL < 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
Emerging drug resistance if virological failure	Week 48
Treatment Digestive tolerance	Week 48
Change from baseline in blood HIV DNA at week 48	Week 48
Treatment adherence	Week 48
Proportions of patients with virological failure (confirmed VL > 50 cp/ml)	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 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

Trial Locations

Locations (1)

Hôpital Saint Louis; 🇫🇷 Paris, France