OBJECTIVES : Heavily treatment experienced (HTE) HIV-1 infected individuals have few if any remaining treatment options, and are at increased risk of progression to AIDS and death. Consequently, there is an urgent need for effective new treatments in this population. The BRIGHTE study demonstrated fostemsavir, a first-in-class oral attachment inhibitor prodrug, significantly reduces mean viral load versus placebo at day 8; indirect comparisons showed long-term improvements in rates of virologic suppression and gains in CD4+ cell count over an optimised regimen alone. This study evaluated the modelled health benefits of management with fostemsavir plus an optimised background therapy (OBT) versus OBT alone.

METHODS : A discrete time Markov state-transition model was developed. Health states were based on CD4+ cell count, viral load, and death. Reflective of the evolving composition of OBT, two matching-adjusted indirect comparisons (MAICs) were conducted to inform comparative effectiveness vs BRIGHTE: data from the BENCHMRK study [1] and the more contemporary VIKING-3 study [2] were used to inform OBT alone outcomes. Event rate and utility profiles were informed by published literature. Independent evaluations estimated life years (LYs) and quality-adjusted life years (QALYs) for the respective MAIC profiles over a lifetime horizon. Health benefits were discounted at 1.5% pa.

RESULTS : Incremental LYs and QALYs for fostemsavir plus OBT vs OBT were estimated to be 1.318 and 1.068 for the BENCHMRK MAIC. For the VIKING-3 MAIC, gains in LY and QALYs of 0.737 and 0.592 were predicted. For both comparisons, incremental gains were attributable to greater time spent in CD4+ cell count states associated with greater immunologic function.

CONCLUSIONS : Fostemsavir is an effective new treatment option predicted to provide meaningful improvements in survival and quality of life for HTE HIV-1 infected individuals. Expected benefits are partly dependent on the composition of OBT, which is highly individualised and determined by available antiretrovirals.