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

ANRS, Emerging Infectious Diseases

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: Darunavir-cobicistat; Drug: Dolutegravir; Drug: Emtricitabine-Tenofovir

Study type: Interventional

Funder types: Other

Identifiers

NCT02987530

ANRS 169

2016-001683-11 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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

Enrollment: 101 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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101 participants in 2 patient groups

Dolutegravir + Emtricitabine/Tenofovir

Experimental group

Description:

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

Treatment:

Drug: Emtricitabine-Tenofovir

Drug: Dolutegravir

Darunavir/Cobicistat + Emtricitabine/Ténofovir

Active Comparator group

Description:

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

Treatment:

Drug: Emtricitabine-Tenofovir

Drug: Darunavir-cobicistat