Understanding the paradox of HIV drugs worsening concurrent tuberculosis

24 September 2015

Neck lymph nodes

Image: Markedly enlarged neck lymph nodes in a woman who developed TB-IRIS during the course of her combined treatment for tuberculosis and HIV-1 infection. Photograph by Graeme Meintjes.

Antiretroviral treatment of HIV-1, the virus that most commonly causes AIDS, can worsen tuberculosis (TB) in patients with both infections. New research has uncovered what's going on at a genetic level to cause this. The work is hoped to lead to ways to prevent or treat the issue.

The study was a collaboration led by Professor Robert Wilkinson and Rachel Lai at the Francis Crick Institute with Professor Graeme Meintjes at the University of Cape Town in South Africa.

Professor Wilkinson (currently based at Mill Hill) said: "HIV-1  infection is a major cause of death throughout the developing world, especially in Africa. HIV-1 weakens the immune system such that other infections become much more common.

"The commonest of all such infections is TB and 20 to 30 per cent of such dually infected people may die. It is known that both HIV-1 and TB must be treated together to reduce this risk. However it's not uncommon for the improvement in immunity caused by antiretroviral treatment of HIV-1 to make TB temporarily worse."

The syndrome is known as the HIV-TB immune reconstitution inflammatory syndrome (TB-IRIS). Investigating how TB-IRIS occurs is important so that it can be prevented or treated, allowing the otherwise beneficial effects of combined antiretroviral and antituberculosis therapies to suppress both infections.

In this study the researchers screened blood samples from patients with HIV-associated TB to look at the expression levels of all their genes. This enabled the scientists to identify a number of genes that were being expressed at unusally high levels called 'Toll-like receptors'. They found that these Toll-like receptors were causing activation of an inflammatory cascade called the inflammasome, which starts an inflammatory process in the body and is associated with TB-IRIS.

Professor Wilkinson said: "This work opens the possibility of finding better ways to predict when TB-IRIS might occur. It also suggests a way to better target therapies to prevent and treat this syndrome."

The paper, The HIV-Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Is Characterized by Toll-Like-Receptor And Inflammasome Signaling, is published in Nature Communications.

  • Francis Crick Institute and University of Cape Town scientists have discovered what's happening at a genetic level that means some patients with HIV and TB who are treated with antiretroviral therapy find that their TB worsens. They hope the findings will lead to better ways to prevent and treat the syndrome.
  • The research was supported by the Medical Research Council, the Wellcome Trust, the European Union and the National Research Foundation of South Africa.