Pharmacokinetics of Maraviroc and Boosted Atazanavir Dual Regimen in Stable HIV-infected Patients

The purpose of this study is to describe pharmacokinetics of maraviroc (MVC) 300 mg and atazanavir/ritonavir (ATV/r) 200/100 mg QD in HIV-infected stable patients.

Study Overview

• Status: Withdrawn
• Conditions: HIV Infection
• Intervention / Treatment: Drug: maraviroc (300 mg QD) + atazanavir/ritonavir (300 and 200 mg /100 mg QD)

Detailed Description

The rational of this study is to save therapeutic options, toxicity and costs. The available literature shows that antiretroviral regimens that do not include a nucleoside backbone of tenofovir resulted in less bone and kidney toxicity. Atazanavir dosing 200/100 mg qd represents a simplification strategy correlated with virologic efficacy and a reduction of parameters toxicity associated. Maraviroc is suggested as a possible drug associated to PI/r in dual therapies. Even in this case, the available evidence supports the choice of the dosage of 300 mg/day.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Torino, Italy
    • University of Torino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age>18 years;
• confirmed HIV-antibodies positivity;
• signed informed consent;
• HIV-RNA <20 cp/ml for the last 24 months;
• no virological failures to PI regimens;
• no major PI resistance associated mutations;
• genotypic tropism for CCR5 co-receptor.

Exclusion Criteria:

• active opportunistic infections or neoplasms;
• need for drugs with known drug-drug interactions with included drugs;
• liver cirrhosis;
• any evidence of tropism for CXCR4 or dual infection;
• pregnancy;
• self-reported adherence<90%;
• HBsAg positivity;
• detectable HCV RNA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MVC + ATV/r; maraviroc (300 mg tablet, 300 mg per day every 24 hours) + atazanavir/ritonavir (300 and 200 mg capsule, 300 and 200 mg per day every 24 hours / 100 mg capsule, 100 mg per day every 24 hours)

Drug: maraviroc (300 mg QD) + atazanavir/ritonavir (300 and 200 mg /100 mg QD); Phase 1: switch from tenofovir disoproxil fumarate/emtricitabine (200/245 mg QD)+ atazanavir/ritonavir (300 /100 mg QD) to maraviroc (300 mg QD) + atazanavir/ritonavir (300 /100 mg QD). Phase 2: switch from maraviroc (300 mg QD) + atazanavir/ritonavir (300 /100 mg QD) to maraviroc (300 mg QD) + atazanavir/ritonavir (200 /100 mg QD); Other Names: CELSENTRI; REYATAZ; NORVIR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maraviroc (300 mg, QD) + atazanavir/ritonavir (200/100 mg, QD) pharmacokinetic evaluation	Number of participants with maraviroc Ctrough>50ng/ml	within the first 16 weeks after switch

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
viral suppression evaluation	Number of participants with HIV-RNA<20 cp/ml	week 60
CD4 count evaluation	Changes in CD4+ count	week 60
bone density evaluation	Changes in bone mineral density (DEXA femur and spine)	week 60
bone metabolism markers evaluation	Changes in bone metabolism markers (bALP and vitamin D, PTH)	week 60
glomerular and tubular renal function evaluation	Changes in proteinuria, glycosuria, phosphaturia and GFR;	week 60
lipid metabolism markers evaluation	changes in total, HDL, LDL cholesterol and triglycerides	week 60
bilirubin evaluation	changes in total bilirubin levels	week 60

Collaborators and Investigators

• Sponsor: University of Turin, Italy

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: October 14, 2018
• First Submitted That Met QC Criteria: October 14, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): November 6, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: ritonavir; maraviroc; atazanavir
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Ritonavir; Maraviroc; Atazanavir Sulfate
• Other Study ID Numbers: MARAT; 2014-004692-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided