Two-pronged treatment can reduce TB safely and effectively, study finds
5 Jun 2014 - 15:30
A trial of isoniazid preventive therapy (IPT) plus antiretroviral therapy (ART) to prevent TB has shown safety and efficacy in patients with HIV, say researchers of a UCT study published in the Lancet. TB is the biggest cause of morbidity & mortality in HIV-infected people 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, with supervision from Professors Gary Maartens and Robert Wilkinson at UCT, and included clinic staff working for Medecins Sans Frontieres and the Western Cape provincial government.
They conducted a trial of IPT plus ART therapy to prevent TB at Khayelitsha site B clinic, Cape Town. The addition of IPT was found to be safe and reduced TB incidence by 37%. The clinical trial shows that the use of isoniazid (INH) reduces the incidence of TB in adults living with HIV who are on anti-retroviral treatment.
“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 Prof Bongani Mayosi, head of Medicine at UCT and Groote Schuur Hospital.
Discussing the purpose of the study, Prof Maartens explains that the risk of TB could be reduced in HIV-infected people not on ART, by using the TB drug isoniazid. However, ART also reduces the risk of TB. It was 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 1329 participants on ART in Khayelitsha in a Provincial Department of Health clinic,” he says.
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 in people not on ART showed that the benefit was only seen in people with positive TSTs.
Maartens says that TB preventive therapy with isoniazid in people with HIV has been under-utilised. Some reasons for this include: TST is difficult to do and the patient has to return after 2-3 days to read the result; follow up and care of people not yet needing ART is challenging to set up (they would typically come to the clinic 6 monthly. By contrast, adding isoniazid to patients already in care 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 World Health Organization (WHO)
The study was funded by the Dept of Health, Medecins Sans Frontieres (MSF), Wellcome Trust & EDCTP, while MSF were key partners in conducting the study.
Dr Rangaka & Prof Robert Wilkinson, Director of Clinical Infectious Diseases Research Initiative (CIDRI) have conducted a series of studies focused on latent TB infection in HIV-infected people. Prof Maartens has also had a longstanding interest in the prevention and diagnosis of TB in HIV infection.
“Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial”. Rangaka MX et al. Lancet. 2014 May 13. pii: S0140-6736(14)60162-8. doi: 10.1016/S0140-6736(14)60162-8. [Epub ahead of print]