A randomised controlled trial of 3 strategies for the treatment of ARV-naive HIV-infected patients with tuberculosis (RAFA)

The overall aim of this project is to build research capacity and networks in West Africa and to conduct clinical trials to assess the effectiveness of three alternative strategies for treating ARV-naive HIV-infected patients with tuberculosis in Benin, Guinea and Senegal.

The main objectives are:

To conduct a phase III randomised controlled trial to assess in ARV-naïve TB/HIV patients with CD4 counts less than 350 cells/mm3 the efficacy in terms of morbidly and mortality of 3 treatment strategies:
early ARV initiation (week 2) with a standard TB treatment,
versus delayed ARV treatment (week 8) with a standard TB treatment,
versus delayed ARV treatment (week 8) with twice the standard dose of rifampicin during the intensive phase of TB treatment (15mg/Kg instead of 10 mg/Kg) and standard TB treatment in the continuation phase.To characterise anti-tuberculosis drug pharmacokinetics among HIV-TB co-infected patients, to assess treatment strategy-related sources of pharmacokinetic variation, and to evaluate differences in pharmacokinetics between patients with different treatment outcomes.To strengthen the research capacities of 3 well-established Tuberculosis Control Programmes to conduct clinical trials, through providing appropriate technology transfer and training (including 1 PhD program and 3 MSc programs), and guidance and mentoring from experienced researchers, in order to create sustainable research capacities.To reinforce the structures and to develop a West African clinical trial TB and TB/HIV network based around sites of excellence for field research in order that in the near future these sites are in a position to initiate, as well as to participate in, further international multicentre trials of new drugs or vaccines.

 The Institute of Tropical Medicine is one of eight trial partners. Specific responsibilities are:

Quality control of all direct sensitivity tests of isolates found to be rifampicin      resistant and 15 % of all rifampicin-susceptible isolates.Performance of molecular tests (MIRU) in patients who develop TB (again) after the end of the TB treatment or during the 12 month follow-up period in order to      differentiate relapse from re-infection.

Project type:PhD project