The Chennai-based National Institute for Research in Tuberculosis (formerly Tuberculosis Research Centre) has started a pilot testing programme of providing for six months isoniazid TB drug as prophylactic to HIV positive individuals. People recruited will include those on antiretroviral therapy (ART) too.
The programme was started about two months ago at six centres in Tamil Nadu (including two ART centres in Chennai) and it got under way recently in Bangalore, New Delhi and Hyderabad. The ART centres were chosen by the National AIDS Control Organisation (NACO).
“For the first six months, the incidence of TB [in HIV positive people] in each of these ART centres will be studied. This will provide us the baseline data,” said Dr. Soumya Swaminathan, Director of the National Institute for Research in Tuberculosis (NIRT), Chennai. “TB is the most common opportunistic infection, and occurs in the first two years in nearly 10 per cent of the people on ART. During the next six months, the volunteers will be given the TB drug and the incidence rate of TB will be compared with the baseline data.”
Only those who do not have TB, are not alcoholic and do not suffer from liver and peripheral neuropathy problems will be recruited for the pilot testing. The sample size will be more than 6,000 HIV positive people across the ART centres.
“The prophylactic effect is expected to continue for another six to 12 months after the six-month treatment with isoniazid,” Dr. Swaminathan said. According to her, there is no additional risk of people developing resistance to the drug when given as a prophylactic for six months. The resistance to isoniazid in the general population is 11-17 pert cent.
“Most studies have not shown an increase in resistance to isoniazid when it is given as a prophylactic,” she stressed. “Even if people develop resistance to the drug, they can be treated with the standard first-line TB-drug regimen. Most of them will respond.”
“Toxicity an issue”
With regard to toxicity — liver and peripheral neuropathy — she said: “it will definitely be an issue. Toxicity will be additive in patients who are having other drugs. But the proportion of people who will develop toxicity is less. Less than 0.5 per cent of them will develop toxicity.”
Way back in 1998, the World Health Organisation recommended six months of isoniazid drug as a TB preventive therapy for people with HIV. It has now come out with two recommendations — six months of preventive therapy and, if possible, countries should extend the period of treatment to 36 months.
Implementation of the WHO recommendations was poor, especially in India as the government wanted Indian data before launching the programme. The NIRT started trial on 712 volunteers and the results are published today (December 15) in PLoS ONE journal. “We presented the results of the trial in 2010 in conferences and to NACO,” she said.
Two-armed trial
The trial had two arms — one had a six-month regimen of isoniazid and ethambutol, and the other comprised a 36-month regimen of isoniazid alone. Both regimens were found to be effective in preventing TB and the 36-month regimen had 40 per cent lower TB incidence. However, the difference between the two arms was not statistically significant.
Though one arm used two drugs for six months, isoniazid will be the only drug used in the pilot testing. According to her, the decision to drop ethambutol was taken on the basis of cost, logistics feasibility and acceptability. “Our study provided the evidence that isoniazid prevention therapy is beneficial in HIV positive people,” she said. “Dropping one drug [ethambutol] does not affect the safety or efficacy. This has been shown in other trials too.”
