Long-term outcomes of fostemsavir in heavily treatment-experienced adults with advanced HIV

Treatment with fostemsavir (FTR) plus optimized background therapy (OBT) is associated with durable virologic response and continuous CD4⁺ T-cell increases in heavily treatment-experienced (HTE) adults with advanced HIV-1 infection and limited treatment options, according to study results presented at IDWeek 2023, held from October 11 to 15, in Boston, Massachusetts.

Researchers examined the long-term efficacy of FTR plus OBT among subgroups of HTE patients with advanced HIV infection who were included in a previous phase 3 trial. The initial phase 3 trial included 371 patients who were failing (HIV-1 RNA >400 copies/mL) their current antiretroviral therapy (ART) regimen and had 2 or fewer fully active and approved ARTs remaining as treatment options for OBT.

Patients with 1 to 2 remaining treatment options were enrolled in a randomized cohort and received open-label FTR plus OBT following an 8-day blinded placebo-controlled period. Patients with no remaining treatment options were enrolled in a nonrandomized cohort and initiated open-label FTR plus OBT at baseline. The researchers compared virologic and immunologic responses between the cohorts, adjusting for baseline demographics and disease characteristics.

A total of 371 patients were included in the analysis, of whom 272 were in the randomized cohort and 99 were in the nonrandomized cohort. Overall, 45% of patients were aged 50 years and older, 78% were men, and 70% were White.

The rate of virologic response was similar across all subgroups and aligned with the overall response rate. Moreover, the efficacy of FTR plus OBT was comparable between patients with 1 vs 2 remaining treatment options. However, reduced response rates were observed among patients in the randomized and nonrandomized cohorts who had either high viral loads or low CD4⁺ T-cell counts at baseline.

In subgroups stratified by age, sex, race, and geographic region, robust and continuous increases in CD4⁺ T-cell count were observed among most patients between weeks and 96 and 240. In addition, the mean change from baseline in CD4⁺ T-cell count was greater than 200 cells/mm³ among all patients enrolled in the randomized cohort.

Similar results were observed in patients with baseline viral loads at or above 100,000 HIV-1 RNA copies/mL, as well as in those with baseline CD4⁺ T-cell counts below 20 cells/mm³.

The researchers noted several limitations, including loss to follow-up, missing data, and study disruptions related to the COVID-19 pandemic.

According to the researchers, “These data highlight the role of FTR as a treatment option for HTE people with multidrug-resistant HIV-1 regardless of demographic or disease characteristics.”

By Lisa Kuhns, PhD

References:

Dyson A, Aberg JA, Molina JM, et al. Durable efficacy and robust CD4+ T-cell count improvement observed across age, race, sex, and geographic subgroups of heavily treatment-experienced people with multidrug-resistant HIV-1 after 240 weeks of fostemsavir treatment. Presented at: IDWeek 2023; October 11-15; Boston, MA. Poster 365.