A daily three-month regimen of isoniazid and pyrazinamide is just as effective at preventing the development of active tuberculosis (TB) as a six-month course of isoniazid in people living with HIV, a Russian study has shown. The findings were presented by Dr Zinaida Zagdyn at the 15th European AIDS Conference in Barcelona on Thursday.
Isoniazid has been shown to prevent the development of active TB in people living with HIV in sub-Saharan Africa who tested positive for TB exposure. However, the six-month course of treatment may be difficult for people to adhere to, and there is interest in reducing the length of the preventive treatment regimen. A three-month course of isoniazid and pyrazinamide is already recommended as an option for TB prevention in Russian guidelines, but clinical trial evidence regarding its efficacy and safety is lacking.
The incidence of TB in people living with HIV in Eastern Europe is very high, and another study presented at the conference showed that people with HIV in the region were four times more likely to die after being diagnosed with TB than people in Latin America or Western Europe, despite receiving a similar course of treatment. Reducing the risk of developing TB is a priority for improving the health of people living with HIV in Eastern Europe.
The St Petersburg TB Research Institute and the Leningrad Regional AIDS Center conducted a randomised clinical trial in 514 consecutive patients recruited from May 2009 to May 2011. Patients were randomised by day of diagnosis, so that 216 people were assigned to receive a three-month regimen of isoniazid and pyrazinamide and 298 to receive a six-month regimen of isoniazid.
Participants were followed for two years after completion of preventive treatment to assess the primary study outcomes of development of active TB or death.
Approximately two thirds of study participants were men (6%), 70% had been exposed to HIV through injecting drug use, and 90% were receiving antiretroviral therapy at the time of TB diagnosis. Eighty per cent of study participants had viral hepatitis.
Seventy-seven per cent of the short-course group and 74.5% of the six-month isoniazid group completed the treatment course, with approximately half of non-completers in each group lost to follow up before the completion of treatment.
After a mean follow up of 28.5 months there was no significant difference in the incidence of active TB (2.7% in the isoniazid group vs 4.8% in the short-course group), although a trend was evident favouring the short-course group in death from TB (1.4% vs 0%, p < 0.01).
There was no significant difference in adverse events (chiefly hepatotoxicity), which occurred in 13.0% of people receiving short-course therapy and in 12.1% of people receiving isoniazid (p = 0.7).
Zagdyn Z, Kovelenov A, Beltyukov A Short-course isoniazid and pyrazinamide compared with 6-month isoniazid for tuberculosis prevention in HIV-infected adults: The Russian Randomized Clinical Trial.15th European AIDS Conference, Barcelona, abstract PS2/3, 2015.