A study from East Africa, conducted before HIV infection influenced treatment, the role of a companion drug in the continuation phase was assessed.
Patients with fully susceptible organisms could be treated successfully with isoniazid alone in the continuation phase with few treatment failures and relapses. If there was initial isoniazid resistance, thioacetazone prevented failure in a considerable proportion of cases. However, because of thioacetazone's relative weakness, treatment failures with functional thioacetazone monotherapy were much more frequent than with isoniazid monotherapy. In these cases of failure, resistance to thioacetazone had been acquired by definition. Furthermore, relapses were frequent.
A key concept in the development of a chemotherapy strategy in the context of a national tuberculosis program was the "cascade of regimens". All patients with previously untreated tuberculosis were given a standard first-line regimen, providing the most efficacious drugs in the intensive phase, given under strict observation of drug intake, using hospitalization if needed to ensure it.
In the continuation phase, treatment was self-administered from one-month supplies of the combination tablet isoniazid plus thioacetazone. This approach was chosen because 1) it was not feasible to provide directly observed treatment in the continuation phase, 2) thioacetazone was a very inexpensive drug, 3) if drug resistance was acquired to thioacetazone it didn't matter because the drug was not used in the "fall-back" regimen for patients who failed on treatment.
As expected, a fraction of patients with initial isoniazid resistance will fail on treatment despite the companion drug thioacetazone. By definition, at the point of failure, such patients will have acquired thioacetazone resistance. The next regimen in the "cascade" contained rifampicin throughout the regimen as recommended. It ensured that virtually all patients with a treatment failure to the first-line regimen could be cured as at all times there are at least two drugs present to which the organisms remain susceptible. |
