The Phase IV trial started in June 2006 to treat patients simultaneously for both TB and HIV has returned some important results. The trial once again reinforced the need to treat the afflicted for both the diseases simultaneously.
According to earlier guidelines, patients were to be treated for TB before treatment for AIDS could begin. Unfortunately 20 per cent of patients die in the first year, and another 20 per cent in the second year in the absence of AIDS treatment. This necessitated a change in the strategy — treat patients for AIDS even as TB treatment is under way.
The cure rates
This trial is proof that treating both the diseases at the same time is good for patients. The cure rate was 90 per cent when patients were treated for both the diseases. Compare this with the earlier strategy of treating only for TB, even when co-infected with HIV. The cure rate was at best 72 per cent. The low cure rate when treated only for TB was because many were dying or failing to respond to TB treatment.
“The lower cure rate [when only TB was treated] was probably due to progression of AIDS,” said Dr. Soumya Swaminathan, Senior Deputy Director (Division of HIV/TB), Tuberculosis Research Centre, Chennai. Dr. Swaminathan was the trial investigator. Apart from the cure rate, only five of the 119 patients in the trial died compared with 9-10 per cent mortality as reported in other studies when only TB was treated.
This trial provided the answers to some of the critical issues as well. It was earlier considered that TB symptoms would flare up when a person with TB was given antiretroviral therapy (ART) for AIDS.
Also, treating patients with Nevirapine (an AIDS drug) when already on Rifamycin, a TB drug, would be a problem. That is because Rifamycin induces some enzymes which in turn metabolise Nevirapine. Hence the level of Nevirapine in the blood drops, making it very favourable for HIV to mutate and develop drug resistance.
Apart from showing that it was indeed possible to treat for both the diseases simultaneously, the trial showed the safety and possibility of using Nevirapine even when the patient was on Rifamycin.
The trial had two arms (groups). One arm was given Efavirenz plus two other AIDS drugs and the other got Nevirapine and two other AIDS drugs. Both the arms got the TB drug, Rifamycin.
“Our study showed that it is indeed safe to give Nevirapine when on Rifamycin,” said Dr. Swaminathan. “Nevirapine also brought down the mortality.”
While the HIV viral load in both the arms saw a reduction to less than 400 copies per ml, the percentage of people who showed the reduction was as high as 85 in the case of the arm that got Efavirenz. It was 67 per cent in the arm that got Nevirapine.
The unexpected finding was that the cure rate was 84 per cent in the case of patients who got Nevirapine. The Efaviranz arm had cure rate of 95 per cent.
“The reason for the poor performance [in the case of Nevirapine arm] could most likely be drug interaction between Rifamycin and Nevirapine,” she said. Only 200 mg of Nevirapine is given during the first two weeks before increasing it to 400 mg. “The poor performance could be due to the suboptimal levels of Nevirapine in the blood during the first two weeks of treatment,” she said.
Despite the reduced efficacy, Nevirapine is the best bet in certain cases — pregnant women and psychiatric patients cannot be given Efaviranz.