Reducing TB in HIV patients through two-pronged approach

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A trial of isoniazid preventive therapy (IPT) plus antiretroviral therapy (ART) to prevent TB has shown safety and efficacy in patients with HIV, says the report. TB is the biggest cause of morbidity and mortality in people infected with HIV in Africa. Both IPT and ART protect against TB in HIV-infected people, but it was not known if the two would give additive protection or could be safely combined.

The research team was spearheaded by Dr Molebogeng Rangaka and included clinic staff working for Médecins Sans Frontières (MSF) and the Western Cape Provincial Government, with supervision from Professor Gary Maartens and Professor Robert Wilkinson at UCT. They conducted a trial of IPT in people on ART to prevent TB at Khayelitsha Site B Clinic in Cape Town. The addition of IPT was found to be safe and to reduce TB incidence by 37%.

The clinical trial shows that the use of isoniazid reduces the incidence of TB in adults living with HIV who are on ART.

"These findings will change clinical practice and contribute immensely to the reduction of the scourge of TB. It is one of the highlights of research in the faculty in recent times," says Professor Bongani Mayosi, head of Medicine at UCT and Groote Schuur Hospital.

Discussing the purpose of the study, Professor Maartens explains that it is well established that the risk of TB could also be reduced by IPT in HIV-infected people not on ART. However, ART also reduces the risk of TB. It was previously unknown whether isoniazid would give additional benefit and whether it was safe in patients on ART. "Therefore we did a placebo-controlled, randomised trial, involving 1 329 participants on ART in Khayelitsha in a provincial Department of Health clinic."

The results showed that 12 months of isoniazid reduced the risk of TB significantly (by 37%) and was well tolerated. Importantly, it showed that the benefit was not limited to people with positive tuberculin skin tests (TST) - all prior studies, which were done in people not on ART, showed that the benefit was only seen in people with positive TSTs.

Therapy underutilised

Professor Maartens says that TB-preventive therapy with isoniazid in people with HIV has been underutilised. Some reasons for this include:

• TST is difficult to do and the patient has to return after two or three days to read the result;
  
• follow-up and care of people not yet needing ART is challenging to set up

By contrast, adding isoniazid to patients already in care and receiving regular ART is very easy to implement - an additional advantage is that a TST does not have to be done. These findings have already resulted in modified policy by the national Department of Health.

The Department of Health, MSF, Wellcome Trust and the European and Developing Countries Clinical Trials Partnership funded the study, while MSF were key partners in conducting the study.

Dr Rangaka and Professor Wilkinson, director of the Clinical Infectious Diseases Research Initiative, have conducted a series of studies focused on latent TB infection in HIV-infected people. Professor Maartens has also had a longstanding interest in the prevention and diagnosis of TB in HIV infection.