The authors note that while their findings provide evidence that may influence future treatment guidelines, other factors will need to be taken into consideration before any decision is taken. They stress that their study could not take into account the potential effect of poor quality services on the emergence of rifampicin resistance during the continuation phase. If patients experience relapse of TB after the induction phase while receiving isoniazid and ethambutol, they can receive a rifampicin-containing induction regimen again. If continuation phase treatment with rifampicin fails and patients develop resistance to rifampicin, they will require more complex treatment for multi-drug resistant TB.
In a letter to WHO and the Stop TB Partnership issued this week, treatment advocates urged WHO to move forward with new recommendations on TB treatment following the results of the trial.
“Switching continuation phase regimens from isoniazid/ethambutol to isoniazid/rifampicin should be priority, especially in areas – such as the former Soviet states – with high rates of baseline resistance to isoniazid – and in others with high rates of TB/HIV coinfection.”
They say that the Strategic and Technical Advisory Group for Tuberculosis recommended that WHO release updated TB guidelines incorporating the new findings. The treatment advocates, who attended the 4th Global Stop TB Partnership TB/HIV Working Group in Addis Ababa in September, claim that some country TB programmes are resisting the change due to `programme inertia` and reluctance to implement a further four months of directly observed rifampicin-based therapy.
However isoniazid and rifampicin are the two most potent drugs in the TB arsenal. Many fear that if these two drug are given for four months without direct observed therapy, there is a danger that a patient will be poorly adherent, and develop multi-drug resistant TB, which is both very difficult and expensive to treat. The key reason for preferring the six month continuation phase with INH and ethambutol is that it is felt that the treatment can be given to the patient on a monthly out-patient basis, without directly observed therapy (which taxes already overburdened health care infrastructures). In other words, they fear that directly observed therapy for 6 months, rather than DOTS (2 months) would triple the direct observation workload for already struggling programmes.
In its 2003 recommendations on TB treatment (Guidelines for national programmes. WHO, 2003. p. 34), WHO noted that six month continuation phase was ”particularly appropriate for countries with limited public health care access and unable to organize a system of direct observation through health facilities, community health workers or volunteers.”
Treatment advocates argue that antiretroviral therapy has provided other models that seem highly effective at encouraging adherence, and that national programmes could step up community-based adherence support for TB treatment if they invest in community-based treatment literacy programmes and building a cadre of community TB treatment supporters.
Some countries have already adopted different treatment protocols based on treatment with isoniazid and rifampicin in the continuation phase which are designed to limit the human resource burden of directly observed treatment. In South Africa's National TB Control Programme, for example, some treatment centres carry out TB treatment using a five month continuation phase in which isoniazid and rifampicin are given three times a week. Other centres give rifampicin and isoniazid five times a week during the four month continuation phase, and also give the induction regimen for five days out of seven during the first two months.
HIV & AIDS Treatment in Practice Editor Theo Smart contributed to this report.