ACT HIV TRIAL (2023) Summary and Key Points In 2023, a significant study titled the “ACT HIV TRIAL” was published, which delved into the potential benefits of using adjunctive dexamethasone for the treatment of tuberculous meningitis in HIV-positive adults. This double-blind, randomized, placebo-controlled trial was meticulously designed to establish the safety and efficacy of the drug in this specific patient group.
The main goal was to ascertain if dexamethasone could make a meaningful difference for HIV-positive adults (≥18 years of age) diagnosed with tuberculous meningitis. This clinical condition is particularly challenging given the immunocompromised status of the patients and the severe complications associated with the disease.
A total of 520 patients were enrolled, with inclusion criteria that encompassed adults (18 years or older) who were HIV-infected, had a clinical diagnosis of TBM (with ≥5 days of meningitis symptoms and CSF abnormalities), and were either planning to undergo or had already begun anti-tuberculosis chemotherapy. Intervention:
Participants were split into two groups:
- Dexamethasone group with 263 participants
- Placebo group with 257 participants
The crux of the study was to determine the rate of death from any cause during the 12 months post-randomization. The dexamethasone group exhibited a 44.1% rate, whereas the placebo group had a slightly higher rate at 49%. However, this difference was not statistically significant with a P-value of 0.22. Secondary Outcomes:
The study also probed into the cases of immune reconstitution inflammatory syndrome in the first 6 months post-treatment. The outcomes were similar between the two groups. Furthermore, the research explored serious adverse events, with 73% of the dexamethasone group and 75.5% of the placebo group experiencing at least one such event (P-value: 0.52). Conclusion:
Despite the rigorous methodology and the promising nature of dexamethasone as a potential adjunct therapy, the ACT HIV TRIAL concluded that for HIV-positive adults grappling with tuberculous meningitis, dexamethasone did not provide a significant benefit in terms of survival or other secondary endpoints compared to placebo. The study’s findings were pivotal in guiding treatment approaches for this patient demographic, emphasizing the relentless pursuit of effective therapeutic strategies for some of the most vulnerable populations. It underscored the importance of evidence-based medicine, even when initial hypotheses might seem promising. Source:
Joseph Donovan et al., published in the NEJM, 2023; 389:1357-1367.