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

• ClinicalTrials.gov Identifier: NCT02987530
• Recruitment Status: Completed
• First Posted: December 9, 2016
• Last Update Posted: January 4, 2022
• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborator: Institut National de la Santé Et de la Recherche Médicale, France
• Information provided by (Responsible Party): ANRS, Emerging Infectious Diseases

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: Dolutegravir; Drug: Darunavir-cobicistat; Drug: Emtricitabine-Tenofovir	Phase 3

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 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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Actual Study Start Date: April 11, 2017
• Actual Primary Completion Date: July 30, 2019
• Actual Study Completion Date: January 31, 2020

Arms and Interventions

Arm	Intervention/treatment
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; Oral use, 50mg/day; Other Name: Tivicay; Drug: Emtricitabine-Tenofovir; Oral use, Emtricititabine : 200mg/day Ténofovir : 245mg; 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; Oral use, 800-150mg/day; Other Name: Rezolsta; Drug: Emtricitabine-Tenofovir; Oral use, Emtricititabine : 200mg/day Ténofovir : 245mg; Other Name: Truvada

Outcome Measures

Primary Outcome Measures :

1. HIV-DNA levels in the peripheral blood mononuclear cell (PBMC) at week 48 [ Time Frame: week 48 ]

Secondary Outcome Measures :

1. Cumulative cellular viremia up to week 48 [ Time Frame: week 48 ]
2. Cumulative plasmatic viremia (HIV-1 RNA) at week 48 [ Time Frame: week 48 ]
3. Cumulative plasmatic viremia using the values obtained by ultrasensitive quantification for all HIV-1-RNA values < 50 copies / mL. [ Time Frame: week 48 ]
4. 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 ]
5. 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 ]
6. 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 ]
7. 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 ]
8. Total DNA-HIV levels measured in PBMC: changes between week 0 and week 48. [ Time Frame: between week 0 and week 48 ]
9. CD4 and CD8 counts and percentage 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 ]
10. CD4 and CD8 counts and percentage changes between week 0 and week 48. [ Time Frame: between week 0 and week 48. ]
11. CD4/CD8 ratio 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 ]
12. CD4/CD8 ratio changes between week 0 and week 48. [ Time Frame: between week 0 and week 48. ]
13. 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 ]
14. 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 ]
15. 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 ]
16. Reported quality of life using self-administered questionnaire (PROQOL-HIV questionnaire). [ Time Frame: between week 0 and week 48 ]
17. 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 ]
18. 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 ]
19. Evolution of Metabolic disorders assessed by measurement of cholesterol, triglycerides, blood glucose and lipase [ Time Frame: between week 0 and week 48 ]
20. Evolution of Renal function assessed by urea and serum creatinine. [ Time Frame: between week 0 and week 48 ]
21. Adherence to treatments using self-administered questionnaires [ Time Frame: week 4, week 8, week 12, week 24, week 36 and week 48 ]
22. Adherence to treatments using pills' counts by local pharmacist [ Time Frame: week 4, week 8, week 12, week 24 and week 36 ]
23. Adherence to treatments using MEMS (Medical Event Monitoring System) data collected during the first 3 months [ Time Frame: between week 0 and week 12 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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 inclusion visit will be taken into account. If the Enzyme Linked ImmunoSorbent Assay (ELISA) test result does not dissociate the signals antibodies and p24 antigen or in case of rapid test result :

  • Negative ELISA / rapid test and positive HIV-1 RNA confirmed by a second positive HIV-1 RNA.
  • Positive ELISA / rapid test and WB-HIV1 [0-5] band (s) or IB-HIV-1 [0-3] 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) or IB-HIV-1 [0-3] 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:

• Any antiretroviral treatment (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

Locations

France

All The Regions Of The Country (40 Centers), France

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

• Principal Investigator: Antoine Chéret, MD, PhD; Hôpital Bicêtre

More Information

• Responsible Party: ANRS, Emerging Infectious Diseases
• ClinicalTrials.gov Identifier: NCT02987530
• Other Study ID Numbers: ANRS 169; 2016-001683-11 ( EudraCT Number )
• First Posted: December 9, 2016
• Last Update Posted: January 4, 2022
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ANRS, Emerging Infectious Diseases:

primary infection

Additional relevant MeSH terms:

Infections; Communicable Diseases; Disease Attributes; Pathologic Processes; Tenofovir; Emtricitabine; Dolutegravir; Darunavir; Cobicistat; Cobicistat mixture with darunavir; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors