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National Multicenter Trial Evaluating Two Treatments in Patients With Primary Human Immunodeficiency Virus (HIV-1) Infection (OPTIPRIM-2)

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified December 2016 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT02987530
First received: November 30, 2016
Last updated: December 8, 2016
Last verified: December 2016
  Purpose
The purpose of this study is to compare the impact of two combination of two tablets once daily: dolutegravir associated with emtricitabine / tenofovir versus darunavir / cobicistat associated with emtricitabine / tenofovir on DNA HIV measured in PBMC at 48 weeks in patients with primary HIV-1 infection.

Condition Intervention Phase
HIV-1 Infection Drug: Dolutegravir Drug: Darunavir-cobicistat Drug: Emtricitabine-Tenofovir Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Multicenter Randomized Trial Evaluating in Patients at the Time of the Primary HIV-1 Infection, the Impact on the Viral Reservoir of a Combination Including Tenofovir/Emtricitabine and Dolutegravir or Tenofovir/Emtricitabine and Darunavir/Cobicistat

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • HIV-DNA levels in the peripheral blood mononuclear cell (PBMC) at week 48 [ Time Frame: week 48 ]

Secondary Outcome Measures:
  • Cumulative cellular viremia up to week 48 [ Time Frame: week 48 ]
  • Cumulative plasmatic viremia (HIV-1 RNA) at week 48 [ Time Frame: week 48 ]
  • Cumulative plasmatic viremia using the values obtained by ultrasensitive quantification for all HIV-1-RNA values < 50 copies / mL. [ Time Frame: week 48 ]
  • Levels of HIV-1 RNA in plasma at week 2, week 4, week 8, week 12, week 24, week 36, week 48 and changes between week 0 and week 48 [ Time Frame: week 2, week 4, week 8, week 12, week 24, week 36, week 48 ]
  • Percentage of patients with HIV-1 RNA <50 copies / mL at week 2, week 4, week 8, week 12, week 24, week 36, week 48 [ Time Frame: week 2, week 4, week 8, week 12, week 24, week 36, week 48 ]
  • Proportion of patients with HIV-1-RNA plasma below the ultrasensitive technique quantification threshold at week 2, week 4, week 8, week 12, week 24, week 36 and week 48 [ Time Frame: week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ]
  • Total DNA-HIV levels measured in PBMC at week 2, week 4, week 8, week 12, week 24, week 36 and week 48 [ Time Frame: week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ]
  • Total DNA-HIV levels measured in PBMC: changes between week 0 and week 48. [ Time Frame: between week 0 and week 48 ]
  • CD4 and CD8 counts and percentage at week 4, week 8, week 12, week 24, week 36, week 48. [ Time Frame: week 4, week 8, week 12, week 24, week 36, week 48 ]
  • CD4 and CD8 counts and percentage changes between week 0 and week 48. [ Time Frame: between week 0 and week 48. ]
  • CD4/CD8 ratio at week 4, week 8, week 12, week 24, week 36, week 48. [ Time Frame: week 4, week 8, week 12, week 24, week 36, week 48 ]
  • CD4/CD8 ratio changes between week 0 and week 48. [ Time Frame: between week 0 and week 48. ]
  • Pharmacokinetic: mean concentrations between week 0 and week 48 will be linked to plasma RNA-VIH and DNA-VIH decrease. [ Time Frame: between week 0 and week 48 ]
  • Pharmacokinetic: cumulative AUC between week 0 and week 48 will be linked to plasma RNA-VIH and DNA-VIH decrease. [ Time Frame: between week 0 and week 48 ]
  • Trial treatments tolerance using self-administered questionnaires of symptoms experienced. [ Time Frame: week 0, week 4, week 8, week 12, week 24, week 36 and week 48 ]
  • Reported quality of life using self-administered questionnaire (PROQOL-HIV questionnaire). [ Time Frame: between week 0 and week 48 ]
  • Number, nature and time of occurrence of stage 3 or 4 clinical and biological adverse events (using ANRS scale to grade severity of adverse events in adults). [ Time Frame: between week 0 and week 48 ]
  • HIV infection progression defined by occurrence of B or C stage clinical events or death between week 0 and week 48 [ Time Frame: between week 0 and week 48 ]
  • Evolution of Metabolic disorders assessed by measurement of cholesterol, triglycerides, blood glucose and lipase [ Time Frame: between week 0 and week 48 ]
  • Evolution of Renal function assessed by urea and serum creatinine. [ Time Frame: between week 0 and week 48 ]
  • Adherence to treatments using self-administered questionnaires [ Time Frame: week 4, week 8, week 12, week 24, week 36 and week 48 ]
  • Adherence to treatments using pills' counts by local pharmacist [ Time Frame: week 4, week 8, week 12, week 24 and week 36 ]
  • Adherence to treatments using MEMS (Medical Event Monitoring System) data collected during the first 3 months [ Time Frame: between week 0 and week 12 ]

Estimated Enrollment: 100
Study Start Date: January 2017
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dolutegravir + Emtricitabine/Tenofovir
Patients will take Dolutegravir 50 mg (= Tivicay, 1 tablet per day) with Emtricitabine 200 mg / Ténofovir 245 mg (=Truvada, 1 tablet per day) for 48 weeks
Drug: Dolutegravir
Other Name: Tivicay
Drug: Emtricitabine-Tenofovir
Other Name: Truvada
Active Comparator: Darunavir/Cobicistat + Emtricitabine/Ténofovir
Patients will take Darunavir 800 mg / Cobicistat 150 mg (=Rezolsta, 1 tablet per day) + Emtricitabine 200 mg / Ténofovir 245 mg (=Truvada, 1 tablet per day) for 48 weeks
Drug: Darunavir-cobicistat
Other Name: Rezolsta
Drug: Emtricitabine-Tenofovir
Other Name: Truvada

Detailed Description:

Phase III, randomized (1: 1), comparative, superiority, open-label, parallel assignment, national multicenter trial evaluating two treatments in patients with primary HIV-1 infection.

Comparison of the two combinations regarding:

  • Viral reservoir at W48
  • Early inhibition of viral replication,
  • Plasmatic and cellular cumulative viremia at W48,
  • Immune reconstitution with CD4, CD8 levels and CD4 / CD8 ratio,
  • Activation parameters decrease,
  • Adherence to treatments,
  • Treatments tolerance,
  • Adverse events,
  • Quality of life (by self-administered questionnaires). Study of the pharmacokinetics / dynamics relationship of the decay of plasma, cellular, rectal and spermatic compartments' viral loads.

    50 participants per group will be enrolled in 40 sites in France. Co- inclusion in ANRS CO 06 PRIMO cohort will be offered

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years at screening visit.
  • Patients with primary HIV-1 infection: Any results achieved in the previous 10 days of screening will be taken into account. If the Enzyme Linked ImmunoSorbent Assay (ELISA) test result does not dissociate the signals antibodies and p24 antigen:

    • Negative ELISA and positive HIV-1 RNA confirmed by a second positive HIV-1 RNA.
    • Positive ELISA and WB-HIV1 [0-5] band (s) confirmed by a positive HIV-1 RNA.

If the ELISA test result dissociated p24 antigen and antibodies signals:

  • ELISA Ac - / p24 - and positive HIV-1 RNA confirmed by a second positive HIV-1 RNA.
  • ELISA Ac - / p24 + confirmed by a positive HIV-1 RNA.
  • ELISA Ac + / p24 + or - and WB-HIV1 [0-5] band (s) confirmed by a positive HIV-1 RNA.

    • Written informed consent signed by the person and the investigator no later than the day of the screening visit and before any exam performed in the trial (article L1122-1-1 Public Health Code).
    • Affiliate or beneficiary of a social security system (Article L1121-11 of the Public Health Code) (the State Medical Aid or AME is not a social security system).
    • Patients followed in selected centers, accepting additional constraints and having signed a consent, will participate to virological, immunological and pharmacological sub-studies.
    • Patient agreeing to participate in the trial for 1 year according to the defined terms.

Exclusion Criteria:

  • Treatment with Truvada® (for Pre-Exposure Prohylaxis or Post-exposure prophylaxis) during the 4 weeks preceding inclusion.
  • Associated pathology with urgent care needed.
  • Prothrombin Ratio < 50%.
  • Creatinine clearance < 70 mL / min (Cockroft).
  • aspartate transaminase (AST), alanine transaminase (ALT), or bilirubin (total and conjugated) ≥ 10 times the upper limit of normal.
  • Patient with isolated HIV-2 viral strain.
  • Women of childbearing potential without effective contraception method (see appendix A6).
  • Pregnant or breastfeeding women.
  • Person under legal guardianship or deprived of liberty by a judicial or administrative decision.
  • Patient participating in another research evaluating other treatments with an exclusion period ongoing at the screening visit.
  • Planned absence which could prevent optimal trial participation (vacation abroad, moving, imminent job change ...).
  • Co-administration of prohibited treatments (see § 9.5).
  • History or presence of allergy to the study drugs or their components;
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
  • Any symptoms or laboratory values suggesting a systemic disorder (renal, hepatic, cardiovascular, pulmonary) or other medical conditions that could interfere with the interpretation of trial results or compromise the health of patients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02987530

Contacts
Contact: Fanny Cardon 33 1 53 94 60 36 fanny.cardon@anrs.fr
Contact: Vincent Meiffrédy, MD 33 1 45 59 52 06 vincent.meiffredy@inserm.fr

Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: Antoine Chéret, MD Hôpital Bicêtre
  More Information

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT02987530     History of Changes
Other Study ID Numbers: ANRS 169
2016-001683-11 ( EudraCT Number )
Study First Received: November 30, 2016
Last Updated: December 8, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
primary infection

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Emtricitabine
Darunavir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Dolutegravir
Cobicistat
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on July 26, 2017