Pharmacokinetics of Efavirenz in the Presence of Rifampicin and Isoniazid

Summary

The purpose of the study is to measure the drug levels in the blood of HIV-infected individuals taking anti- HIV medication efavirenz 400 mg once daily in the presence of anti-TB medication rifampicin and isoniazid. The study is being run in two-stages - London (Stage 1) and Kampala (Stage 2).

In London (Stage 1): HIV-1 infected patients (without tuberculosis infection) on established treatment with a combination based on 600 mg efavirenz dose will be recruited.

In Kampala (Stage 2): Patients with both HIV-1 and tuberculosis infection being treated with 600 mg efavirenz combination for HIV AND undergoing TB treatment with a dual therapy regimen contaning rifampicin and isoniazid will be recruited.

Efavirenz-containing regimens are recommended as first-line therapy for HIV-TB co-infected patients. It has been shown there is a lack of a significant difference between efavirenz 400 mg and efavirenz 600 mg, indicating that 400 mg efavirenz is non-inferior to the standard dose.

The advantages of antiretroviral dose reductions may translate into greater benefits for more individuals infected by HIV globally, since they may allow access programs to reach higher numbers of infected patients and compensate for the finite global manufacturing capacity and increasing demand. For efavirenz, significant price reductions have been achieved through elimination of trade, logistics and manufacturing capacity barriers, and further price reductions could be achieved with a significant reduction in the cost of pharmaceutical ingredients. However, no data on the PK and effectiveness of efavirenz 400 mg once daily during TB treatment has been produced. Given that many patients on Efavirenz- based ART will need to be treated for TB during their lifetime and rifampicin is one of the most commonly used treatment for tuberculosis, it is important to study the reduced dose under carefully monitored conditions prior to roll out of a lower dose standard treatment. Therefore, we aim to investigate the PK of efavirenz 400 mg once daily in HIV-infected individuals in the presence of rifampicin and isoniazid in London, UK and in HIV/TB-co-infected individuals on dual anti-TB treatment in Kampala, Uganda

Conditions

• HIV

Interventions

DRUG

Efavirenz

Efavirenz 400mg

DRUG

tenofovir /emtricitabine

tenofovir 245 mg/emtricitabine 200mg

DRUG

tenofovir/lamivudine

tenofovir 245mg/lamivudine 300mg

DRUG

lamivudine/zidovudine

lamivudine 300mg/zidovudine 600mg

DRUG

Rifinah or local generics

Rifampicin 600 mg and isoniazid 300 mg if ≥50kg or rifampicin 450 mg and isoniazid 300 mg if \<50kg.)

Sponsors & Collaborators

• Mylan Inc.

  collaborator INDUSTRY

• United States Agency for International Development (USAID)

  collaborator FED

• St Stephens Aids Trust

  lead OTHER

Principal Investigators

• Marta Boffito, MBBS,MD,PhD · St. Stephen's AIDS Trust

• Mohammed Lamorde, MBBS,MRCP,PhD · Infectious Diseases Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-11-21

Primary Completion

2018-01-31

Completion

2018-02-28

Countries

• Uganda
• United Kingdom

Study Locations