Pilot Study of Maraviroc/Raltegravir for Naive HIV-1 Patients (NNNB)

Association Pour la Recherche en Infectiologie

Status and phase

Unknown

Phase 2

Conditions

HIV

Treatments

Drug: MVC/RAL/FTC/TDF followed by Maraviroc/Raltegravir

Study type

Interventional

Funder types

Other

Identifiers

NCT01291459

2009/HD/01

Details and patient eligibility

About

Background and Rationale

Raltegravir and Maraviroc, the first in class of 2 new families of antiretroviral drugs have demonstrated a high potency in treatment experienced and naive patients. Both drugs appeared well tolerated with low metabolic toxicity. No data are currently available concerning the combination of these 2 drugs.

Hypothesis

Maraviroc + Raltegravir should be potent enough to maintain virological efficacy in naive patients infected by CCR5 HIV-1 previously treated for 6 months with a Maraviroc-Raltegravir-Tenofovir-Emtricitabine combination.

Full description

Objectives:

To establish the ability of a Maraviroc-Raltegravir combination to maintain HIV-1 viral load < 50 copies/ml at week 48 in naive patients infected by CCR5 HIV-1, following an initial 6 month phase of Maraviroc-Raltegravir-Tenofovir-Emtricitabine combination (Intent to treat and strategy analysis)
To study CD4 progression from baseline to week 48
To study the time to virological failure during the simplification phase of the study (from week 24 to week 48)
To study the proportion of patients with HIV RNA < 50 copies/ml at each time point
To study the kinetics of viral load decrease from baseline to week 12
To study the kinetics of proviral DNA decrease from baseline to week 12, 24, 36 and 48
To study the clinical and biological tolerance of Maraviroc-Raltegravir combination through week 48

Study Design/ Clinical Plan

Pilot, multicenter, national, uncontrolled study

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥ 18 years old at the run-in visit
HIV-1 infection
Antiretroviral treatment-naive
CD4 ≥ 200 /mm3
HIV- RNA ≥ 1000 copies/ml
HIV-RNA ≤ 100,000 copies/ml
Antiretroviral therapy is indicated according to current guidelines
CCR5-tropic virus according to the Trofile ES® assayGeno2Pheno algorithm using a predefined false positive rate of 20%
No significant NRTI, NNRTI or PI resistance mutation
Freely-given, written, informed consent obtained; the patient and investigator have signed the consent form (by the latest on the day of the run-in visit and before performing any examinations required by the trial)
Patient covered by a French national health insurance scheme

Exclusion criteria

Women of child-bearing potential not using effective contraception (barrier method)
Pregnant or breast-feeding women
Patients under the age of 18 years
Patients deprived of liberty by a judicial or administrative, hospitalized patients without consent, patients admitted to a health or social purposes other than research
Persons major subject of a measure of legal protection or unable to consent
Previous antiretroviral therapy (with the exception of post-exposure prophylaxis if HIV serology is negative > 3 months after the last dose of antiretroviral drugs)
CXCR4-tropic virus, dual/mixed-tropic virus or undetermined tropism on screening
Presence of significant NRTI, NNRTI or PI resistance mutation(s)
Infection or co-infection with HIV-2, or group O or N HIV-1
Acute phase of an opportunistic infection
Undergoing treatment for tuberculosis
Undergoing chemotherapy and/or radiotherapy for neoplastic disease
Decompensated cirrhosis (Child-Pugh class B or C)
HIV-HBV co-infection. Patients with HIV-HCV co-infection are permitted to participate in the absence of decompensated cirrhosis (Child-Pugh class B or C), of hepatocytolysis > 3 times the upper limit of normal and if treatment for HCV during the ensuing 12 months is not indicated. PAtients with occult HBV are excluded.( positive AcHBc, negative AcHBs, negative AgHBs, positive HBV DNA)
Co-administration of prohibited treatments (see the SPCs of each product) Laboratory parameters: Haemoglobin < 7g/dl, neutrophil count < 500/mm3, platelet count < 50,000/mm3, creatinine clearance < 50 ml/min, alkaline phosphatase, AST, ALT or bilirubin ≥ 3 times upper limit of normal
Patient refuses to participate