Reducing tuberculosis among HIV-infected patients

A trial of isoniazid preventive therapy, or IPT, plus antiretroviral therapy to prevent tuberculosis has shown safety and efficacy in patients with HIV, say researchers at the University of Cape Town in a study published in The Lancet last month.

Tuberculosis, or TB, is the biggest cause of morbidity and mortality in people infected with HIV in Africa.

Both IPT and antiretroviral therapy protect against tuberculosis 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 and the Western Cape provincial government, with supervision from professors Gary Maartens and Robert Wilkinson at the University of Cape Town.

They conducted a trial of IPT on people undertaking antiretroviral therapy to prevent TB at a 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 antiretroviral therapy.

“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 the department of medicine at the University of Cape Town and Groote Schuur Hospital.

Maartens says it is well established that the risk of TB can be reduced by IPT in HIV-infected people not on antiretroviral therapy. However, antiretroviral therapy also reduces the risk of TB although it was previously unknown whether isoniazid would give additional benefit and whether it was safe in patients on antiretroviral therapy.

“Therefore we did a placebo-controlled, randomised trial, involving 1,329 participants on antiretroviral therapy 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 and was well tolerated. Importantly, it showed that the benefit was not limited to people with positive tuberculin skin tests or TST: all prior studies on people not on antiretroviral therapy showed that the benefit was only seen in people with positive skin tests.

Maartens says that TB-preventive therapy with isoniazid in people with HIV has been under-utilised. Some reasons for this include the fact that TST is difficult to do and that the patient has to return after two or three days to read the result. In addition, follow-up and care of people not yet needing antiretroviral therapy is challenging to set up.

By contrast, adding isoniazid to patients already in care and receiving regular antiretroviral therapy is 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.