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

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.

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.

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.