HIV-TB coinfection management remains a global challenge and requires careful drug interaction consideration and monitoring.  This trial aimed to evaluate the efficacy, safety, and pharmacokinetics of co-formulated bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) given twice daily versus standard of care (e.g., tenofovir DF/lamivudine/dolutegravir plus a stand-alone evening dose of dolutegravir) for adults with HIV (CD4 > 50 cells/µL and not on ART) receiving rifampicin-based tuberculosis therapy in South Africa.  Participants in the bictegravir group underwent pharmacokinetic pre- and post-dose sampling at weeks 4, 12, and 32, with a subset additionally undergoing “semi-intensive” sampling.  At week 24, 75/80 (94%) people in the bictegravir group and 40/42 (95%) in the dolutegravir group had HIV RNA < 50 copies/mL.  At week 48, 76/80 (95%) and 39/42 (93%) were suppressed < 50 copies/mL.  Serious adverse events occurred in 14% of bictegravir group participants vs. 7% in the dolutegravir group, however none of the serious events were deemed related to study treatment.  Tuberculosis-associated IRIS occurred in 28% of participants in the bictegravir group vs. 36% in the dolutegravir group.  There were no treatment discontinuations or drug switches due to adverse events, and the vast majority achieved a successful tuberculosis treatment outcome.  No emergent INSTI mutations were observed.

BIC/F/TAF is not currently available in Africa and many resource-limited settings, but the co-formulation has a number of features which make it attractive for expanded global roll-out (i.e. favorable safety profile for children, older adults, and people with kidney or bone disease; small pill size, high barrier to resistance).  Although this study was not powered to determine differences between study groups, the high 24- and 48-week viral suppression rates – as well as the overall reassuring safety observations from this study population – provide compelling evidence to increase access to this therapeutic option.