HIV-associated drug-resistant TB: expanded treatment options and emerging threats

To summarize recent advances in drug-resistant tuberculosis (DR-TB) treatment for people with HIV (PWH), including drug-drug interactions, investigational medications and host-directed therapy, as well as emerging evidence on novel treatment regimens, post-TB complications, and DR-TB medication resistance among PWH.

Treatment for DR-TB has evolved to shorter, all-oral regimens with reduced drug-drug interactions. However, emerging dolutegravir resistance may necessitate protease inhibitor-based ART regimens resulting in interactions that complicate DR-TB management. Investigational TB medications including BTZ-043, sutezolid, and delpazolid demonstrate promising bactericidal activity in early phase trials. Several clinical trials have demonstrated the efficacy of 6-9 month DR-TB regimens and have included PWH; however, all successful shortened regimens currently contain bedaquiline, which limits options for PWH in areas with emerging bedaquiline resistance. While treatments targeting Mycobacterium tuberculosis are the mainstay of treatment, host-directed therapy is being evaluated both as an intervention for treatment and for the prevention of immune reconstitution inflammatory syndrome and post-tuberculosis lung disease.

Treatment options for DR-TB have improved dramatically with less toxic, more effective regimens, but managing HIV-associated DR-TB continues to require careful attention to drug-drug interactions and HIV related co-morbidities. Research into novel DR-TB regimens, especially for people with bedaquiline resistance, and host-directed therapies are critical to realize continued improvement in HIV-associated DR-TB outcomes.