Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)
Primary Purpose
HIV-1 Infections
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
raltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine
darunavir; ritonavir; emtricitabine/tenofovir
Sponsored by
About this trial
This is an interventional treatment trial for HIV-1 Infections focused on measuring Primary HIV-1 infection, antiretroviral treatment, HIV reservoirs, HIV-DNA levels, randomized, Treatment Naive
Eligibility Criteria
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
Sites / Locations
- Hôpital Gustave Dron
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
arm 1
arm 2
Arm Description
darunavir, ritonavir, emtricitabine/tenofovir, maraviroc, raltegravir
darunavir, ritonavir, emtricitabine/tenofovir
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Plasma HIV-RNA levels and proportion of patients with plasma viral load < 50 copies/ml at M12, M24 and M30
Plasma HIV-RNA levels and proportion of patients with plasma viral load < 5 copies/ml at M24
Changes in cell-associated HIV-DNA between baseline and M24
Evolution of the CD4 and CD8 between D0 and M24
Tolerability of trial treatments
Number and type of ARV mutations in virological failures and change in CCR5 tropism
Full Information
NCT ID
NCT01033760
First Posted
December 15, 2009
Last Updated
February 4, 2014
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Gilead Sciences, Merck Sharp & Dohme LLC, Pfizer, Janssen-Cilag Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01033760
Brief Title
Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)
Official Title
Optimisation of Primary HIV1 Infection Treatment (ANRS 147 OPTIPRIM)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Gilead Sciences, Merck Sharp & Dohme LLC, Pfizer, Janssen-Cilag Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infections
Keywords
Primary HIV-1 infection, antiretroviral treatment, HIV reservoirs, HIV-DNA levels, randomized, Treatment Naive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
arm 1
Arm Type
Experimental
Arm Description
darunavir, ritonavir, emtricitabine/tenofovir, maraviroc, raltegravir
Arm Title
arm 2
Arm Type
Active Comparator
Arm Description
darunavir, ritonavir, emtricitabine/tenofovir
Intervention Type
Drug
Intervention Name(s)
raltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
darunavir; ritonavir; emtricitabine/tenofovir
Intervention Description
darunavir (Prezista®): 800 mg QD. ritonavir tablet (Norvir®): 100 mg QD. tenofovir/emtricitabine (Truvada®): one 245/200 mg tablet QD.
Primary Outcome Measure Information:
Title
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
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Plasma HIV-RNA levels and proportion of patients with plasma viral load < 50 copies/ml at M12, M24 and M30
Time Frame
30 months
Title
Plasma HIV-RNA levels and proportion of patients with plasma viral load < 5 copies/ml at M24
Time Frame
24 months
Title
Changes in cell-associated HIV-DNA between baseline and M24
Time Frame
24 Months
Title
Evolution of the CD4 and CD8 between D0 and M24
Time Frame
24 months
Title
Tolerability of trial treatments
Time Frame
24 months
Title
Number and type of ARV mutations in virological failures and change in CCR5 tropism
Time Frame
24 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antoine CHERET, PH
Organizational Affiliation
Tourcoing Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Caroline LASCOUX-COMBE, PH
Organizational Affiliation
Saint Louis Hospital, Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Laurence MEYER, Professor
Organizational Affiliation
Methodologist, INSERM U1018
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Bruno HOEN, Professor
Organizational Affiliation
Saint Jacques Hospital, CHU Besançon
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Isabelle RAVAUX, PH
Organizational Affiliation
Conception Hospital, Marseille
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christine ROUZIOUX, Professor
Organizational Affiliation
Virology Investigator, Necker Hospital Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alain VENET, PH
Organizational Affiliation
Immunology Investigator, INSERM U1012 Bicêtre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daniel OLIVE, Professor
Organizational Affiliation
Immunology Investigator, Cancerology Institut Marseille
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gianfranco PANCINO, PH
Organizational Affiliation
Immunology Investigator, Pasteur Institut Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brigitte AUTRAN, Professor
Organizational Affiliation
Immunology Investiigator, INSERM U543 Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Gustave Dron
City
Tourcoing
ZIP/Postal Code
59208
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
28708873
Citation
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.
Results Reference
derived
PubMed Identifier
25701561
Citation
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.
Results Reference
derived
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Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)
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