Wong Chen Seong

This late-breaker session presented findings from recent studies evaluating treatment strategies for multi-drug resistant tuberculosis (MDR-TB) and cryptococcal meningitis. Regimens containing bedquiline, pretomanid and linezolid are highly efficacious, even at shorter durations. Single dose liposomal amphotetericin B in combination with other antifungals is an effective cryptococcal meningitis induction treatment option.

In the TB-PRACTECAL trial evaluating treatment regimens for MDR-TB, recruitment was terminated early as interim analyses of the primary outcome (treatment failure, death, treatment discontinuation, recurrence of TB, or loss to follow-up) strongly favoured PRACTECAL-1 (24-week bedaquiline, pretomanid, linezolid, moxifloxacin), driven by high rates of treatment discontinuations in SoC arm. Approximately 25% of participants were HIV co-infected. Plans are underway to scale up the regimen. The ZeNix trial evaluated treatment regimens for X/MDR-TB comprising 6 months of bedaquiline and pretomanid and varying doses and durations of daily linezolid (1200mg for 6 months; 1200mg for 2 months, 600mg for 6 months, 600mg for 2months). High success rates of the primary endpoint of relapse-free cure were observed for all regimens in a cohort with 19.9% HIV co-infected. This confirms the efficacy of the BPaL regimen, allowing treatment with reduced doses and durations of linezolid, which resulting reduced toxicity. The Ambition-cm trial evaluated the efficacy of single high-dose (10mg/kg) liposomal amphotericin-B (AmBisome) compared to 7 daily doses of amphotericinB deoxycholate (1mg/kg) in combination with flucytosine and fluconazole for induction treatment of HIV-associated cryptococcal meningitis. The single high-dose AmBisome was non-inferior in averting all-cause mortality at 10 weeks, with fewer severe adverse effects.

Highly effective novel strategies are urgently needed in the treatment armamentarium for MDR-TB and cryptococcal meningitis, which still contribute significantly to morbidity and mortality in PLHIV globally. The use of lower dose and shorter durations of combination antituberculous and antifungal combination regimens respectively are likely to have great clinical impact, particularly given their proven efficacy and reduced toxicity profiles. There is a need to ensure these therapies are affordable and accessible, particularly in resource-limited settings where these diseases are particularly prevalent, and where attributable morbidity and mortality are still high.