Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)

Optimisation of Primary HIV1 Infection Treatment (ANRS 147 OPTIPRIM)

The purpose of this trial is to assess the impact of raltegravir, maraviroc, darunavir/r, and Truvada® (emtricitabine/tenofovir) vs. darunavir/r and Truvada® on cell-associated HIV-DNA levels in patients with primary HIV-1 infection.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infections
• Intervention / Treatment: Drug: raltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine; Drug: darunavir; ritonavir; emtricitabine/tenofovir

Detailed Description

Primary HIV-1 infection is characterized by a phase of intense replication, with a quick dissemination and early changes in the immune system. During primary HIV-1 infection, damages to MALT and GALT promotes a chronic cell activation, which participates in a progressive decay of immune functions.

After HAART initiation, the magnitude and rapidity of cell-associated HIV-DNA decrease are significantly higher in patients with primary HIV-1 infection than in patients with chronic infection (Ngo Giang Huong, AIDS 2004).

We hypothesize that an early intervention at different levels of viral replication with potent and well-tolerated new drugs may have a greater impact on cell-associated HIV-DNA levels than conventional triple-drug HAART.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Tourcoing, France, 59208
    • Hôpital Gustave Dron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with acute or primary HIV-1 infection
• Acute infection: negative or slightly positive Elisa, with negative or incomplete western-blot (0 or 1 antibody) and positive HIV-RNA and/or positive Ag p24.
• Primary infection: positive Elisa with incomplete Western-blot (≥ 2 and < 5 antibodies with the presence of anti-p24 antibodies associated with an anti-gp160 or an anti-gp120 or an anti-gp41antibody) and positive HIV-RNA.
• Symptomatic Primary infection or CD4 <500/mm3
• written informed consent
• ≥ 18 years old

Exclusion Criteria:

• Prior post exposure antiretroviral treatment within six months before enrolment
• Pregnancy or breast-feeding
• HIV-2 infection
• Current malignancy
• Prothrombin time < 50%
• Creatinine clearance < 60 ml/min
• ASAT, ALAT or bilirubin ≥10*N
• Platelets < 25000/mm3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: arm 1; darunavir, ritonavir, emtricitabine/tenofovir, maraviroc, raltegravir	Drug: raltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine; raltegravir (Isentress®): 400 mg bid. maraviroc (Celsentri®): 150 mg bid. darunavir (Prezista®): 800 mg QD. ritonavir tablet (Norvir®): 100 mg QD. tenofovir/emtricitabine (Truvada®): one 245/200 mg tablet QD.
Active Comparator: arm 2; darunavir, ritonavir, emtricitabine/tenofovir	Drug: darunavir; ritonavir; emtricitabine/tenofovir; darunavir (Prezista®): 800 mg QD. ritonavir tablet (Norvir®): 100 mg QD. tenofovir/emtricitabine (Truvada®): one 245/200 mg tablet QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare the 24-month impact of maximized vs. conventional HAART- on HIV reservoirs, as assessed by cell-associated HIV-DNA levels, in patients with acute or primary HIV-1 infection	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma HIV-RNA levels and proportion of patients with plasma viral load < 50 copies/ml at M12, M24 and M30	30 months
Plasma HIV-RNA levels and proportion of patients with plasma viral load < 5 copies/ml at M24	24 months
Changes in cell-associated HIV-DNA between baseline and M24	24 Months
Evolution of the CD4 and CD8 between D0 and M24	24 months
Tolerability of trial treatments	24 months
Number and type of ARV mutations in virological failures and change in CCR5 tropism	24 Months

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Merck Sharp & Dohme LLC; Pfizer; Gilead Sciences; Janssen-Cilag Ltd.
• Investigators: Principal Investigator: Antoine CHERET, PH, Tourcoing Hospital; Principal Investigator: Caroline LASCOUX-COMBE, PH, Saint Louis Hospital, Paris; Study Chair: Laurence MEYER, Professor, Methodologist, INSERM U1018; Principal Investigator: Bruno HOEN, Professor, Saint Jacques Hospital, CHU Besançon; Principal Investigator: Isabelle RAVAUX, PH, Conception Hospital, Marseille; Principal Investigator: Christine ROUZIOUX, Professor, Virology Investigator, Necker Hospital Paris; Principal Investigator: Alain VENET, PH, Immunology Investigator, INSERM U1012 Bicêtre; Principal Investigator: Daniel OLIVE, Professor, Immunology Investigator, Cancerology Institut Marseille; Principal Investigator: Gianfranco PANCINO, PH, Immunology Investigator, Pasteur Institut Paris; Principal Investigator: Brigitte AUTRAN, Professor, Immunology Investiigator, INSERM U543 Paris

Publications and helpful links

General Publications

• Cheret A, Durier C, Melard A, Ploquin M, Heitzmann J, Lecuroux C, Avettand-Fenoel V, David L, Pialoux G, Chennebault JM, Muller-Trutwin M, Goujard C, Rouzioux C, Meyer L; ANRS OPTIPRIM study group. Impact of early cART on HIV blood and semen compartments at the time of primary infection. PLoS One. 2017 Jul 14;12(7):e0180191. doi: 10.1371/journal.pone.0180191. eCollection 2017.
• Cheret A, Nembot G, Melard A, Lascoux C, Slama L, Miailhes P, Yeni P, Abel S, Avettand-Fenoel V, Venet A, Chaix ML, Molina JM, Katlama C, Goujard C, Tamalet C, Raffi F, Lafeuillade A, Reynes J, Ravaux I, Hoen B, Delfraissy JF, Meyer L, Rouzioux C; OPTIPRIM ANRS Study Group. Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial. Lancet Infect Dis. 2015 Apr;15(4):387-96. doi: 10.1016/S1473-3099(15)70021-6. Epub 2015 Feb 18.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 15, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimate): December 16, 2009

Study Record Updates

• Last Update Posted (Estimate): February 5, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: antiretroviral treatment; Treatment Naive; randomized; HIV reservoirs; Primary HIV-1 infection; HIV-DNA levels
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; HIV Infections; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Maraviroc; Darunavir
• Other Study ID Numbers: 2009-014742-28; EudraCT (Registry Identifier: 2009-014742-28)