03:05pm Wednesday 12 December 2018

Infectious diseases treatment breakthrough

University of Cape Town (UCT) scientists have offered the first hope of addressing the risk of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS), which is common among HIV-positive patients also taking anti-tuberculosis medication.

To date, there has been no management strategy for preventing this complication. But now the findings provide clinicians with a strategy for reducing this risk, Professor Graeme Meintjes, principal investigator on the so-called PredART trial, said of the results which were published in the latest edition of the respected New England Journal of Medicine.

The Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), based at UCT, conducted the trial at Khayelitsha’s Site B HIV-TB clinic. The scientists worked in collaboration with colleagues at the Institute of Tropical Medicine (ITM) in Antwerp, Belgium.

According to their analysis, a four-week course of moderate-dose immune suppressant prednisone reduces by 30% the risk of TB-IRIS in HIV-positive patients taking anti-TB medication, who are at risk for developing the condition.

Meintjes explained that it is critical to start patients with HIV, TB and very low CD4 counts on antiretrovirals within the first two weeks of treatment for TB – “because it saves lives”.

Inflammatory complication

“But this also comes at the cost of a two-fold higher risk of them developing the inflammatory complication TB-IRIS,” he said.

 

“The researchers found that patients who received prednisone during the first four weeks of ART were less likely to develop TB-IRIS than those who received the placebo.”

TB-IRIS is characterised by severe inflammation which occurs shortly after patients on TB treatment also start taking antiretroviral therapy (ART). It’s a serious risk that results in a quarter of affected patients being hospitalised.

The PredART researchers investigated whether administering moderate-dose prednisone, which modulates the immune system and treats inflammation, can safely reduce the incidence of paradoxical TB-associated IRIS in patients at high risk for the syndrome.

The trial involved 240 HIV-positive patients with very low CD4 counts who were initiating ART, and who had started TB treatment within the 30 days prior to enrolment.

The CD4 count offers a snapshot of the health of the immune system, with CD4 cells the white blood cells that fight infection. The count usually increases when the HI virus is controlled with ART.

“The researchers found that patients who received prednisone during the first four weeks of ART were less likely to develop TB-IRIS than those who received the placebo,” Meintjes said.

A total of 56 patients in the placebo group were diagnosed with TB-associated IRIS, against 39 in the prednisone group, indicating a risk reduction of 30%. Moderate-dose prednisone was also well tolerated by the patients, and the researchers found no evidence of an increased risk of severe infections or cancers with this treatment.

“This is the first trial to show that TB-IRIS can be prevented in these patients, and represents an important contribution to the body of knowledge on management of HIV-TB co-infection,” said Meintjes.

Read the full publication.

 

University of Cape Town

 


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