The use of fostemsavir in heavily treatment-experienced patients with HIV-1 was found to be associated with sustained virologic response rates through 96 weeks of treatment, according to the results of a study published in AIDS.
BRIGHTE (ClinicalTrials.gov Identifier: NCT02362503) is an ongoing phase 3 clinical trial studying fostemsavir and optimized background therapy in heavily treatment-experienced patients with HIV-1 (N=371) in whom their current antiretroviral regimen was ineffectual, with limited treatment options available. The randomized cohort was composed of 272 patients and the nonrandomized cohort was composed of 99 patients; participants were enrolled at 108 international investigational sites from February 2015 through May 2016. The most common agents used as initial optimized background therapy in the randomized cohort were dolutegravir (229/272, 84%), darunavir (134/272, 49%), and tenofovir disoproxil fumarate (116/272, 43%).
In the randomized cohort, patients with at least 1 remaining fully active drug in at least 1 but no more than 2 antiretroviral classes at baseline were randomly assigned to receive blinded fostemsavir 600 mg twice daily or placebo concomitantly with their failing regimen from day 1 to day 8. After day 8, all patients were given open-label fostemsavir along with their optimized background therapy. In the nonrandomized cohort, patients with no fully active drugs were given open-label fostemsavir on day 1 and were allowed to co-enroll in other investigational antiretroviral trials.
In the randomized cohort, the number of patients with HIV-1 RNA <40 copies/mL increased from 144 (53%) at week 24 to 163 (60%) at week 96. Among the subgroups, virologic response rates were sustained, and there were no clear differences based on demographic characteristics. Mean increase in CD4+ T-cell count from baseline was 205 cells/µL. This increase was generally observed across all subgroups with the following exceptions: a greater mean increase of 292 cells/µL was reported in patients younger than 35 years (95% CI, 225-359) compared with the mean increase of 166 cells/µL reported in patients aged 35 years to less than 50 years (95% CI, 133-199); and a greater mean increase of 306 cells/µL was reported in patients from Europe (95% CI, 219-392) compared with the mean increase of 147 cells/µL in patients from North America (95% CI, 112-182).
The investigators noted comparable safety across subgroups for the combined cohorts with diarrhea, nausea, upper respiratory tract infection, and headache being the most common adverse events. There was a total of 24 deaths between the 2 cohorts.
The following limitations of this study are inherent to trials conducted in heavily treatment-experienced patients who have highly individualized treatment needs: small sample size; single-arm study design; and broad diversity of background regimen.
“Subgroup analyses of the Week 96 BRIGHTE data for the Randomized Cohort show robust and sustained efficacy with fostemsavir across a wide spectrum of heavily treatment-experienced adults with HIV-1 and limited treatment options. These results support fostemsavir as a therapeutic option that may be uniquely suited to address the needs of the heavily treatment-experienced population,” the study authors concluded.
Ackerman P, Thompson M, Molina J-M, et al. Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1. AIDS. Published online June 1, 2021. doi:10.1097/QAD.0000000000002851