Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Optimisation of Primary HIV1 Infection Treatment (ANRS 147 OPTIPRIM)

Conditions
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HIV-1 Infections

Intervention / Treatment
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* Drug: raltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine
* Drug: darunavir; ritonavir; emtricitabine/tenofovir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arm 1<br>darunavir, ritonavir, emtricitabine/tenofovir, maraviroc, raltegravir | Drug: raltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine<br>* 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.<br>|
| Active Comparator: arm 2<br>darunavir, ritonavir, emtricitabine/tenofovir | Drug: darunavir; ritonavir; emtricitabine/tenofovir<br>* darunavir (Prezista®): 800 mg QD. ritonavir tablet (Norvir®): 100 mg QD. tenofovir/emtricitabine (Truvada®): one 245/200 mg tablet QD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary HIV-1 infection, antiretroviral treatment, HIV reservoirs, HIV-DNA levels, randomized, Treatment Naive