Fostemsavir may improve inflammatory biomarkers in HTE adults with MDR HIV

Treatment with fostemsavir and optimized background therapy (OBT) may improve inflammatory biomarkers in heavily treatment-experienced (HTE) adults with multidrug-resistant (MDR) HIV infection, according to results of a study published in Open Forum Infectious Diseases.

The findings come from an ongoing, 2-cohort, international phase 3 trial of HTE adults with MDR HIV infection. Researchers aimed to investigate the mean log₁₀ change in HIV viral load as well as changes in CD4⁺ T-cell count and CD4⁺/CD8⁺ ratios in patients failing their current antiretroviral treatment (ART) regimen (HIV-1 RNA, ≥400 copies/mL) who had at least 2 fully active and approved antiretrovirals available at screening.

At enrollment, patients with 1 or 2 fully active antiretrovirals available were randomly assigned 3:1 to receive either fostemsavir 600 mg twice daily or placebo in addition to their current ART regimen for 8 days, followed by a transition to fostemsavir plus OBT. Patients with no fully active antiretrovirals available were assigned to a nonrandomized cohort. No formal statistical analyses were performed.

A total of 272 patients were included in the randomized cohort, of whom the median age was 48 (range, 18-73) years, 74% were men, and 68% were White. The median CD4⁺ count was 100 (range, 0-1160) cells/mm³; 199 (73%) patients had a count below 200 cells/mm³ and 97 (36%) had a count below 50 cells/mm³. In addition, 212 (78%) patients had a CD4⁺/CD8⁺ ratio of less than 0.30, and the median viral load for the overall cohort was 4.66 (range, 1.59-6.91) log₁₀ copies/mL.

At the start of the open-label fostemsavir plus OBT period, 142 (52%) and 114 (42%) patients had 1 and 2 fully active antiretrovirals available, respectively, whereas the remaining 16 (6%) patients had none. The most common agent for initial OBT among the cohort was dolutegravir (84%), followed by emtricitabine or lamivudine (50%), darunavir (49%), and tenofovir disoproxil fumarate (42%).

After 96 weeks, the mean baseline CD4⁺ count among patients in the randomized cohort (152 cells/mm³) increased by a mean of 205 cells/mm³. Similar results were observed for CD4⁺/CD8⁺ ratio, with a mean increase of 0.24 from baseline. The researchers noted higher CD4⁺ counts across all patient subgroups as well as an increased percentage of patients with CD4⁺/CD8⁺ ratios above 0.45 between baseline and week 96 (from 9.0% to 40%).

Further analysis between baseline and week 96 showed reduced values for the inflammatory biomarkers sCD14 (mean [SD] change, -738.2 [981.8] µg/L), sCD163 (mean change, -138.0 [193.4] µg/L), and D-dimer (mean change, -0.099 [0.521] mg/L fibrinogen-equivalent units). Similar changes were observed across all demographic subgroups. In women, D-dimer levels increased numerically at 24 and 48 weeks with high variability and then declined below baseline levels at week 96. The researchers also noted numerical improvements in biomarkers at week 96 regardless of virologic response (HIV-1 RNA, <40 copies/mL), protocol-derived virologic failure, or baseline CD4⁺ count.

Study limitations include the exploratory nature of the analysis, the population of predominantly White men, and the lack of a control group and formal statistical analyses.

According to the researchers, “Future research will aim to assess the changes in other biomarkers of systemic inflammation in HTE persons with HIV-1 treated with fostemsavir + OBT and the clinical relevance of these changes…”

Disclosure: This study was supported by ViiV Healthcare, and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Paul Basilio

References:

Clark A, Prakash M, Chabria S, et al. Inflammatory biomarker reduction with fostemsavir over 96 weeks in heavily treatment-experienced adults with multidrug-resistant HIV-1 in the BRIGHTE Study. Open Forum Infect Dis. Published online August 26, 2024. doi:10.1093/ofid/ofae469