Clinical trial NCT01033760: Optimisation of Primary HIV1 Infection Treatment(ANRS 147 OPTIPRIM)
Official title: Optimisation of Primary HIV1 Infection Treatment (ANRS 147 OPTIPRIM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infections
Keywords: Primary HIV-1 infection
antiretroviral treatment
HIV reservoirs
HIV-DNA levels
randomized
Treatment Naive
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Gilead Sciences
name: Merck Sharp & Dohme LLC
name: Pfizer
name: Janssen-Cilag Ltd.
First posted: 2009-12-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 24 months
Secondary outcomes:
measure: Plasma HIV-RNA levels and proportion of patients with plasma viral load < 50 copies/ml at M12, M24 and M30
timeFrame: 30 months
measure: Plasma HIV-RNA levels and proportion of patients with plasma viral load < 5 copies/ml at M24
timeFrame: 24 months
measure: Changes in cell-associated HIV-DNA between baseline and M24
timeFrame: 24 Months
measure: Evolution of the CD4 and CD8 between D0 and M24
timeFrame: 24 months
measure: Tolerability of trial treatments
timeFrame: 24 months
measure: Number and type of ARV mutations in virological failures and change in CCR5 tropism
timeFrame: 24 Months
Other outcomes:
Locations:
city: Tourcoing
country: France
facility: Hôpital Gustave Dron
Study officials:
affiliation: Tourcoing Hospital
name: Antoine CHERET, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint Louis Hospital, Paris
name: Caroline LASCOUX-COMBE, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Methodologist, INSERM U1018
name: Laurence MEYER, Professor
role: STUDY_CHAIR
affiliation: Saint Jacques Hospital, CHU Besançon
name: Bruno HOEN, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Conception Hospital, Marseille
name: Isabelle RAVAUX, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Virology Investigator, Necker Hospital Paris
name: Christine ROUZIOUX, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Immunology Investigator, INSERM U1012 Bicêtre
name: Alain VENET, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Immunology Investigator, Cancerology Institut Marseille
name: Daniel OLIVE, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Immunology Investigator, Pasteur Institut Paris
name: Gianfranco PANCINO, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: Immunology Investiigator, INSERM U543 Paris
name: Brigitte AUTRAN, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.