Clinical impact of antiretroviral agents used in optimized background therapy with fostemsavir in heavily treatment-experienced adults with HIV-1: exploratory analyses of the phase 3 BRIGHTE study


BACKGROUND: BRIGHTE is an ongoing phase 3 study investigating fostemsavir plus optimized background therapy (OBT) in heavily treatment-experienced (HTE) individuals.
METHODS: In the Randomized Cohort (RC; N=272), participants with fully active agents (FAAs) in only 1 or 2 remaining antiretroviral (ARV) classes received fostemsavir 600 mg BID (n=203) or placebo (n=69) for 8 days followed by open-label fostemsavir plus OBT. The Non-randomized Cohort (NRC; N=99), participants with 0 approved FAAs, received fostemsavir 600 mg BID plus OBT from Day 1. This post hoc analysis evaluated most common ARVs and their association with Week 96 virologic response (HIV-1 RNA <40 copies/mL).
RESULTS: Most participants were men (289/371; 78%), aged <50 (206/371; 56%), and white (259/371; 70%). RC participants had lower mean number of agents in initial OBT (3.6 vs 4.7, respectively) and higher mean number of FAAs vs the NRC (1.4 vs 0.2, respectively). Across both cohorts, integrase inhibitors (most notably dolutegravir BID) were included in OBT (Table 1). Protease inhibitors, particularly darunavir BID, and nucleoside reverse transcriptase inhibitors were more commonly used in the NRC than RC (Table 1). In the RC, Week 96 virologic response rates were comparable regardless of presence or absence of core ARV agent, except for dolutegravir (presence: 64%, absence: 40%; Table 2).

CONCLUSIONS: The OBT of HTE participants in BRIGHTE was highly individualized but most commonly included dolutegravir BID. Fostemsavir plus OBT yielded strong rates of virologic response through Week 96 in this population with extensive multidrug-resistant HIV-1 and limited remaining treatment options.