Nevirapine Drug Levels in HIV Positive Patients Also Receiving Rifampicin for Tuberculosis

NCT00617643 | Completed Phase 4 DMC

• 1 other identifier: CPR 004
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Triomune is the most commonly prescribed treatment for HIV infection in Uganda. Triomune is manufactured by a generic drug company and consists of three drugs combined in a single pill given twice daily (stavudine 30mg plus lamivudine 150mg plus nevirapine 200mg). It is known that the levels of nevirapine in a patient's blood are highest in the first two weeks of treatment. Therefore it is recommended that patients starting on nevirapine should undergo dose escalation i.e start on 200mg once daily for two weeks and then increase to full dose of 200mg twice daily in order to avoid nevirapine related rash. It is not possible to do dose escalation with a fixed dose combination pill like Triomune and for the two weeks of the dose escalation patients either can buy stavudine plus lamivudine plus nevirapine as separate pills or take Triomune in the morning and then take stavudine plus lamivudine as separate pills in the evening. Rifampicin is used to treat TB and lowers the levels of nevirapine in a patient's blood. This raises two questions in routine clinical practice for patients who are co-infected with HIV and TB (1) Do we need to put our patients to the trouble of dose escalation of nevirapine if they are already on rifampicin? and (2) If we dose escalate nevirapine in patients on rifampicin, are we putting them at risk of low drug levels and development of resistance? The aim of this study is to compare the plasma concentrations of nevirapine in HIV infected patients who are commencing antiretroviral therapy with and without a lead in dose of nevirapine and who are also receiving concomitant treatment with antituberculous therapy which includes rifampicin to assess whether dose escalation of nevirapine is appropriate in this patient population

Conditions

HIV Infections; Tuberculosis

Keywords

Nevirapine; Rifampicin; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• To compare the pharmacokinetics of nevirapine with dose escalation and without dose escalation of nevirapine on day 7, 14 and 21 in patients who are on rifampicin therapy.

  12 months

Secondary Outcomes (1)

• Safety and tolerability of nevirapine when administered in HIV-TB coinfected patients receiving rifampicin

  1 month

Study Arms (2)

2

ACTIVE COMPARATOR

Triomune® 30 one tablet once daily (am) plus Zerit® 30 + Epivir 150mg once daily (pm) for two weeks

Drug: Nevirapine initiation with dose escalation

1

EXPERIMENTAL

Triomune® 30 one tablet twice daily for two weeks

Drug: Nevirapine without dose escalation

Interventions

Nevirapine without dose escalation DRUG

Fixed dose combination tablets of stavudine 30mg,lamivudine 150mg and nevirapine tablets 200mg twice daily at initiation of antiretroviral therapy in patients receiving rifampicin for tuberculosis therapy

Also known as: Triomune 30

1

Nevirapine initiation with dose escalation DRUG

Triomune® 30 (according to body weight) one tablet once daily (am) plus Zerit® 30 + Epivir 150mg once daily (pm) for two weeks

2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to provide full informed written consent
• Confirmed diagnosis of HIV infection
• On rifampicin therapy for at least two weeks
• Clinical criteria for commencing antiretroviral therapy

You may not qualify if:

• Hemoglobin \< 8g/dl
• Liver and renal function tests \> 3 times the upper limit of normal
• Pregnancy
• Use of know inhibitors or inducers of Cytochrome P450 or P-glycoprotein.
• Use of herbal medications
• Intercurrent Illness

Sponsors & Collaborators

• Makerere University: lead
• University of Liverpool: collaborator

Study Sites (1)

Infectious Diseases Institute, Faculty of Medicine, Makerere University

Kampala, Uganda

Location

Related Publications (1)

• Lamorde M, Byakika-Kibwika P, Okaba-Kayom V, Ryan M, Coakley P, Boffito M, Namakula R, Kalemeera F, Colebunders R, Back D, Khoo S, Merry C. Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin. J Antimicrob Chemother. 2011 Jan;66(1):180-3. doi: 10.1093/jac/dkq411. Epub 2010 Nov 2.

  PMID: 21047828 DERIVED

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

Nevirapine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Concepta A Merry, PhD

  University of Dublin, Trinity College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 5, 2008
• First Posted: February 18, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: December 1, 2010
• Last Updated: December 6, 2010

Record last verified: 2010-12

Locations

UG (1)