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.