Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)

Official Title: “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.

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.

Intervention(s) in this Clinical Trial

• 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.
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: arm 1
  • darunavir, ritonavir, emtricitabine/tenofovir, maraviroc, raltegravir
• Active Comparator: arm 2
  • darunavir, ritonavir, emtricitabine/tenofovir

Primary 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
  • Time Frame: 24 months
    Safety Issue?: No

Secondary Measures

• Plasma HIV-RNA levels and proportion of patients with plasma viral load < 50 copies/ml at M12, M24 and M30
  • Time Frame: 30 months
    Safety Issue?: No
• Plasma HIV-RNA levels and proportion of patients with plasma viral load < 5 copies/ml at M24
  • Time Frame: 24 months
    Safety Issue?: No
• Changes in cell-associated HIV-DNA between baseline and M24
  • Time Frame: 24 Months
    Safety Issue?: No
• Evolution of the CD4 and CD8 between D0 and M24
  • Time Frame: 24 months
    Safety Issue?: No
• Tolerability of trial treatments
  • Time Frame: 24 months
    Safety Issue?: Yes
• Number and type of ARV mutations in virological failures and change in CCR5 tropism
  • Time Frame: 24 Months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: French National Agency for Research on AIDS and Viral Hepatitis Other

Overall Clinical Trial Officials and Contacts

Antoine CHERET, PH Principal Investigator Font-Pré Hospital Toulon  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01033760

Study ID Number: 2009-014742-28

ClinicalTrials.gov Identifier: NCT01033760

Health Authority: France: Afssaps - French Health Products Safety Agency