A Study on Antiretroviral Therapy (ART) Naïve Patients On Different Regimens to Treat Hiv (NORTHIV)

A Study on ART Naïve Patients On Different Regimens to Treat Hiv (a Phase 4 Study)

The present study aims to compare efficacy, side-effects, and treatment adherence of three different treatment regimens given to antiretroviral naïve HIV-1 infected patients. Treatment will be initiated in accordance with the Swedish National Guidelines. In the twice daily (BID) arm (1), which could be considered as a standard regimen at present, lopinavir/ritonavir, is co-administrated with 2 nucleoside reverse transcriptase inhibitors (NRTIs) administrated BID. The first once daily (QD) arm (2) combines the protease inhibitor (PI) atazanavir/ritonavir with 2 NRTIs administrated QD, and in the second QD arm (3), the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is combined with 2 NRTIs administrated QD. All drugs used in the study are licensed in the participating countries and patients will be followed as in clinical practice. Patients could optionally, after informed consent, be followed with additional measurements of HIV-1 RNA after 1, 2, and 3 weeks of treatment to asses the kinetics of viral decline after initiation of treatment.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Lopinavir ritonavir; Drug: Atazanavir ritonavir; Drug: Efavirenz

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Goteborg, Sweden, S-41685
    • Department of Infectious Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged 16 years of age
• HIV-1 infected as documented by a licensed HIV-1 antibody ELISA
• Ability to understand and provide informed consent
• Indication for antiretroviral treatment
• Antiretroviral naïve
• All clinical laboratory values not clinically significant

Exclusion Criteria:

• Subjects being pregnant
• Women of childbearing potential not practicing birth control
• Subjects with renal failure requiring dialysis
• Drug interactions with any of the study drugs that are not manageable
• Resistance to any of the study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: lopinavir/ritonavir; 400/100 mg BID + 2 NRTIs BID	Drug: Lopinavir ritonavir; 400mg BD 100mg BD
ACTIVE_COMPARATOR: atazanavir/ritonavir; 300mg+100mg QD+ 2 NRTI QD	Drug: Atazanavir ritonavir; 300mg QD 100mg QD
ACTIVE_COMPARATOR: efavirenz; 600mg QD + 2NRTI QD	Drug: Efavirenz; 600mg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intention to treat (ITT)/time to loss of virological response (TLOVR)	Virological failure (see 5.5.2 for definition); Treatment interruption or change of study treatment due to side-effects; Treatment interruption or change of study treatment due to any other reason; Missed to follow-up 1. HIV-1 RNA >50 copies/ml in two consecutive measurements from week 24 and on 2. any rise in HIV-1 RNA >50 copies/ml in two consecutive measurements after viral load <50 copies/ml has been reached 3. HIV-1 RNA never <50 copies/ml after week 24	144 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of abnormal laboratory parameters	Incidence of abnormal laboratory parameters at follow-up	144 weeks
Adherence to study medication	Proportion of doses taken correctly	144 weeks
Frequency of adverse events	Proportion of treatment discontinuations and changes due to different adverse events	144 weeks
Changes in CD4 cell counts	Changes in CD4+ T-cell count from baseline	144 weeks
Changes in plasma lipids	Changes from baseline in plasma lipids	144 weeks
Frequency of hyperlipidemia	Incidence of hypercholesterolemia and hypertriglyceridemia at baseline and follow-up	144 weeks

Collaborators and Investigators

• Sponsor: Göteborg University
• Investigators: Principal Investigator: Magnus Gisslén, Professor, Goteborg Universitet

Publications and helpful links

General Publications

• Eden A, Andersson LM, Andersson O, Flamholc L, Josephson F, Nilsson S, Ormaasen V, Svedhem V, Sall C, Sonnerborg A, Tunback P, Gisslen M. Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naive HIV-1-infected patients. AIDS Res Hum Retroviruses. 2010 May;26(5):533-40. doi: 10.1089/aid.2009.0177.
• Josephson F, Andersson MC, Flamholc L, Gisslen M, Hagberg L, Ormaasen V, Sonnerborg A, Vesterbacka J, Bottiger Y. The relation between treatment outcome and efavirenz, atazanavir or lopinavir exposure in the NORTHIV trial of treatment-naive HIV-1 infected patients. Eur J Clin Pharmacol. 2010 Apr;66(4):349-57. doi: 10.1007/s00228-009-0763-z. Epub 2009 Dec 5.
• Vesterbacka J, Nowak P, Barqasho B, Abdurahman S, Nystrom J, Nilsson S, Funaoka H, Kanda T, Andersson LM, Gisslen M, Sonnerborg A. Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy. PLoS One. 2013;8(1):e55038. doi: 10.1371/journal.pone.0055038. Epub 2013 Jan 28.

Helpful Links

• Goteborg University

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): December 1, 2009
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: September 28, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (ESTIMATE): October 3, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 4, 2011
• Last Update Submitted That Met QC Criteria: October 2, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: HIV; Antiretroviral therapy; efavirenz; lopinavir; atazanavir; randomised controlled clinical trial
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Ritonavir; Lopinavir; Atazanavir Sulfate; Efavirenz
• Other Study ID Numbers: Northiv protocol 3.66