Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, kills around 1.5 million people each year. Tuberculous meningitis is the most lethal form of tuberculosis, killing or disabling more than half of HIV-positive individuals who contract it, despite treatment with the best available anti-tuberculosis drugs for 12 months.
In HIV-negative people with tuberculous meningitis, deaths from the disease are reduced by the addition of the corticosteroid dexamethasone to anti-tuberculosis drug treatment. However, whether dexamethasone saves lives in HIV-positive people with tuberculous meningitis is unknown, although most treatment guidelines recommend it is given.
The trial conducted by OUCRU involved 520 participants from Vietnam and Indonesia. The trial found that the addition of dexamethasone to standard anti-tuberculosis drugs did not reduce the number of adults who died within 12 months from recruitment to the trial. The results of the ACT HIV trial Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-positive Adults were published in the New England Journal of Medicine.
The study underscores the urgent global need for better detection and treatment of HIV and tuberculosis. It also shows the importance of cross-country collaboration between researchers in Vietnam and Indonesia in delivering practice-defining trials.
Over four years, 520 HIV-positive Vietnamese and Indonesian adults with tuberculous meningitis were randomly assigned to receive six to eight weeks of dexamethasone or an identical placebo alongside anti-tuberculosis drugs. There were 116/263 (44.1%) deaths in the dexamethasone group and 126/257 (49.0%) deaths in the placebo group, a difference that was not statistically significant. No other benefits of dexamethasone were identified.
The trial results are important because they show that dexamethasone has little benefit in HIV-positive people with tuberculous meningitis, unlike HIV-negative people. It also highlights the unacceptably high death rate from tuberculous meningitis in HIV-positive people, and the urgent global need to detect and treat HIV and tuberculosis earlier and more effectively.
Dr Nguyen Huu Lan, Director of Pham Ngoc Thach Hospital, said: ‘WHO recommends the use of Dexamethasone for all TBM patients, regardless of their HIV status. This clinical trial provides important evidence for WHO to revise its recommendations for TBM/HIV (+) patients, which will change the practice at local hospitals.’
The trial was a collaboration between researchers at the OUCRU in Vietnam and Indonesia, together with staff at the Hospital for Tropical Diseases and Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease in Ho Chi Minh City, Vietnam, and Dr Cipto Mangunkusumo National Reference Hospital and Persahabatan National Respiratory Referral Hospital, in Jakarta, Indonesia. The trial was funded by Wellcome, UK.