Efavirenz-based Versus Nevirapine-based Antiretroviral Therapy Among HIV-infected Patients Receiving Rifampin (N2R)

The randomized controlled trial is conducted among antiretroviral naive co-infected HIV and tuberculosis patients who receiving rifampicin-based antituberculous regimen fro at least 4 weeks butt not exceed 16 weeks before enrolment. All patients receive the same backbone regimen of stavudine (30 mg/40 mg twice daily)+ lamivudie 150 mg twice daily. They are randomized to receive nevirapine 400 mg/day twice daily vs efavirenz 600 mg/day at bed time. All patients are followed through 144 weeks after initiation of antiviral therapy. The primary objective are to compare the proportion of patient who achieve undetectable plasma HIV-1RNA<50 copies/ml at week 48. The previous reports demonstrated that the standard doses of both nevirapine and efavirenz coulde be used among co-infected HIV and tuberculosis patients who receiving rifampicin even though plasma levels are somewhat reduced by rifampicin. However, there have been not been a randomized control trial to compare these two regimens. Thus, this trial will provide the efficacy data between these two regimens.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: efavirenz; Drug: nevirapine

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-60 years
• Positive Serology for HIV-1
• Naïve to antiretroviral therapy
• Baseline CD4 cell counts <250 cells/mm3
• Diagnosed active tuberculosis by clinical features and/or positive acid fast stain and/or positive culture
• Received rifampicin at least 4 weeks but not exceed 16 weeks prior to enrollment
• Willing to participate and sign inform consent

Exclusion Criteria:

• Aspartate transferase enzymes (AST) or alanine transminase enzyme (ALT) >5 times of upper limit
• total bilirubin >3 times of upper limit
• serum creatinine) >2 times of upper limit
• pregnancy or lactation
• receiving immunosuppressive drugs
• receiving any drugs that may have drug-drug interaction with nevirapine and rifampicin
• chronic alcoholic drunken and intravenous drug users
• Previously received single dose of nevirapine to prevent mother to child transmission
• positive for serum cryptococcal antigen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efavirenz; Efavirenz 600 mg/day + stavudine +lamivudine	Drug: efavirenz; efavirenz 600 mg/day + stavudine + lamivudine
Experimental: Nevirapine; Nevirapine 400 mg/day + stavudine +lamivudine	Drug: nevirapine; nevirapine 400 mg/day + stavudine +lamivudine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare proportion of patients who achieved undetectable plasma HIV-1RNA< 50 copies/mL at 48 weeks after initiation of antiretroviral treatment between the 2 groups	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
to compare CD4 response at 48, 96 and 144 weeks after initiation of antiretroviral treatment, to compare adverse drugs reaction between the 2 groups	144 weeks

Collaborators and Investigators

• Sponsor: Bamrasnaradura Infectious Diseases Institute
• Collaborators: Chulalongkorn University; Mahidol University
• Investigators: Principal Investigator: Weerawat Manosuthi, MD, Bamrasnaradura Infectious Diseases Institute

Publications and helpful links

General Publications

• Manosuthi W, Sungkanuparph S, Tantanathip P, Lueangniyomkul A, Mankatitham W, Prasithsirskul W, Burapatarawong S, Thongyen S, Likanonsakul S, Thawornwa U, Prommool V, Ruxrungtham K; N2R Study Team. A randomized trial comparing plasma drug concentrations and efficacies between 2 nonnucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R Study. Clin Infect Dis. 2009 Jun 15;48(12):1752-9. doi: 10.1086/599114.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: June 5, 2007
• First Submitted That Met QC Criteria: June 5, 2007
• First Posted (Estimate): June 6, 2007

Study Record Updates

• Last Update Posted (Estimate): November 22, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: HIV; tuberculosis; efavirenz; nevirapine; rifampicin; co-infected HIV and tuberculosis patients
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; 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; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Nevirapine; Efavirenz
• Other Study ID Numbers: 210041000824904203