An inexpensive and readily accessible anti-inflammatory drug
reduces the risk of a potentially dangerous complication in
patients starting treatment for both TB and HIV.
The international team which carried out the clinical trial in
South Africa included scientists from the Crick. Their results
provide the first evidence for an effective strategy to prevent
this common complication, which would be an important step in South
Africa and other parts of sub-Saharan Africa dealing with the dual
epidemics of HIV and TB.
In sub-Saharan Africa, people with HIV frequently also develop
TB. People arriving at clinics with TB symptoms are often found to
have both HIV infection and active TB disease.
In these patients with immune systems weakened by HIV, TB
treatment is first started followed by antiretroviral therapy (ART)
for the HIV a few weeks later.
"If you have advanced HIV infection and develop TB, the
mortality rate can be as high as 1 in 4," says Robert Wilkinson of
the Francis Crick Institute and Imperial College London, one of the
study authors.
"Treat the TB, and people begin to get better. Treating the HIV
as well with antiretroviral therapy (ART), you see better outcomes
- more people survive. But in some patients, in some studies up to
40-50%, the TB suddenly gets much worse. The reason is that, in
addition to restoring good immune responses, the ART restores bad
immune responses."
This complication is known as TB-associated immune
reconstitution inflammatory syndrome, or TB-IRIS for short. About a
quarter of patients who develop TB-IRIS require hospital admission
and there are no treatments to prevent it at present.
Robert adds: "A lot of TB damage and even death is down to the
patient's own immune system and inflammation.
"We carried out a trial that randomized patients to steroids as
an anti-inflammatory drug, as well as the TB and HIV treatments.
This is perhaps a surprising approach in HIV patients - we're
looking to immunosuppress them even more. But we wanted to try and
dampen any inflammation that made the TB worse."
The scientists carried out a clinical trial in South Africa to see
if a common, inexpensive steroid called prednisone could safely
reduce the risk of TB-IRIS in these patients.
Prednisone is a corticosteroid anti-inflammatory drug that costs
less than US$3 for a month's supply in South Africa. It is widely
used for the treatment of conditions such as asthma and certain
forms of arthritis.
The trial included 240 patients in HIV-TB clinics in Khayelitsha
township, Cape Town, who were HIV-positive with a low immune cell
count, who had not received ART and had been diagnosed with TB. All
patients received TB treatment and ART.
They were randomized to receive either prednisone or a placebo
for 4 weeks at the same time as they started ART medication. They
were followed intensively for a further 8 weeks.
The proportion of patients diagnosed with TB-IRIS was
significantly lower in the group receiving the steroid. 33% of
patients in the prednisone group developed TB-IRIS compared with
47% of people receiving placebo.
Prednisone appeared safe in these patients with advanced HIV:
adverse events and severe infections were not more common in the
prednisone-treated participants.
The PredART trial was conducted by researchers from
South Africa, Belgium and the UK. It was funded by the European and
Developing Countries Clinical Trials Partnership (EDCTP), the South
African National Department of Science and Technology and
Wellcome.
The results were presented by the principal investigator, Graeme
Meintjes of the University of Cape Town, at the Conference on
Retroviruses and Opportunistic Infections (CROI) in Seattle,
USA on 15 February.