Six- and nine-month courses of TB treatment equivalent in Indian HIV-positive patients

A six-month course of tuberculosis (TB) treatment resulted in a similar cure rate to a nine-month course in HIV-positive patients in India, according to a study presented on Friday at the Twelfth Annual Retrovirus Conference in Boston. This suggests that this approach may help to reduce the cost of TB treatment in resource-limited settings with a high prevalence of HIV.

India carries a third of the global TB burden, with over 60% of the country’s population carrying the latent form of the disease. Coupled with the country’s rising HIV epidemic, with a current prevalence of 5.1 million HIV-positive people (of whom 2.5 million also have TB), cost-effective approaches to the treatment of TB are urgently required to reduce the impact of the two infections.

A recently published randomised study suggested that a six-month course consistnt of two months of intensive induction treatment with four drugs, followed by a four-month continuation phase of daily treatment with isoniazid and rifampicin is superior to a six month continuation phase of isoniazid and ethambutol. However, as most of the patients in this study were HIV-negative, it is unclear if a similar shorter-course protocol is suitable for HIV-positive patients.

To address this issue, Indian researchers at the Tuberculosis Research Centre in Chennai designed a study to compare the efficacy of two regimens:

• Group A: Two months induction therapy with ethambutol, isoniazid, pyrazinamide, pyridoxine and rifampicin, followed by a four-month continuation phase of treatment with three times weekly isoniazid and rifampicin, with the induction phase extended by four weeks if sputum smears were positive at the end of month 2.
• Group B: Two months induction therapy as above, followed by a seven-month continuation phase.

Treatment was directly observed for all doses during the first two months, and then supervised once weekly.

One hundred and fifty-eight HIV-positive adult patients from Chennai and Madurai in southern India were recruited for the study. All the patients had culture-confirmed pulmonary TB, but were receiving no antiretroviral therapy. The patients were randomised to the two treatment groups. Sixty-nine percent of the patients had CD4 cell counts below 200 cells/mm³, and 3% of the patients had multi-drug resistant TB.

One hundred and twenty-two patients were available for evaluation at the end of follow-up, with 93% sputum smear negative in group A and 98% in group B. Mycobacterium tuberculosis culture was negative for 99% of group A and 95% of group B. There were seven relapses in group A and nine in group B. All differences were non-significant.

Adverse events observed during the study were mainly gastrointestinal, but the researchers saw no difference between the two study groups. Similarly, the eleven patients who died during the treatment period, the five who defaulted and the 19 who required a change of regimen were equally distributed between the two treatment groups.

As the study was powered to detect a 20% reduction in ‘unfavourable’ responses, the researchers concluded that the six-month regimen was equivalent to the nine month regimen in HIV-positive patients in India. Soumya Swaminathan, presenting, concluded that the use of this regimen may reduce the cost of treatment, without compromising the control of TB in this heavily co-infected population.