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Clinical Trial
. 2024 Aug 26;11(9):ofae469.
doi: 10.1093/ofid/ofae469. eCollection 2024 Sep.

Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study

Andrew Clark  1 , Manyu Prakash  1 , Shiven Chabria  2 , Amy Pierce  3 , Jose R Castillo-Mancilla  3 , Marcia Wang  4 , Fangfang Du  4 , Allan R Tenorio  2
Affiliations
Clinical Trial

Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study

Andrew Clark et al. Open Forum Infect Dis. .

Abstract

Background: Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1.

Methods: CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening. No formal statistical analyses were performed.

Results: Among 272 participants, increases were observed from baseline to week 96 in CD4+ T-cell count (mean increase, +205 cells/mm3) and CD4+/CD8+ ratio (mean increase, +0.24). The proportion of observed participants with a CD4+/CD8+ ratio ≥0.45 increased from 9% (25/272) at baseline to 40% (85/213) at week 96. From baseline to week 96, we also observed trends toward decreases in the following (mean [SD] change): soluble CD14, -738.2 (981.8) µg/L; soluble CD163, -138.0 (193.4) µg/L; and D-dimer, -0.099 (0.521) mg/L fibrinogen-equivalent units. Decreases in biomarkers were generally observed among subgroups by baseline disease characteristics, virologic response, and CD4+ T-cell count.

Conclusions: These data suggest that heavily treatment-experienced persons with multidrug-resistant HIV-1 treated with fostemsavir + optimized background therapy may have improvements in immune parameters, including markers of monocyte activation and coagulopathy.

Clinical trials registration: NCT02362503 (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT02362503).

Keywords: CD4+ T-cell count; CD4+/CD8+ ratio; biomarkers; fostemsavir; heavily treatment experienced.

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Conflict of interest statement

Potential conflicts of interest. A. C., M. P., S. C., A. P., J. R. C.-M., M. W., F. D., and A. R. T. are or were employees of ViiV Healthcare or GSK at the time of the analysis and may own stock in GSK.

Figures

Figure 1.
Figure 1.
Mean change from baseline: A, CD4+ T-cell count; B, CD4+/CD8+ ratio. Mean change from baseline in CD4+ T-cell count: C, by baseline CD4+ T-cell count; D, by Snapshot virologic outcome at the same time point. a At week 24, 1 participant did not have virologic data in window (mean change in CD4+ T-cell count, +142.0 cells/mm3). At week 96, 2 participants did not have virologic data in window (mean change in CD4+ T-cell count, +290.5 cells/mm3). Snapshot data not available for week 12. Error bars represent SD.
Figure 2.
Figure 2.
Mean change from baseline: A, soluble CD14; B, soluble CD163; C, D-dimer. Error bars represent SD. Reference range was 800 to 3200 µg/L for soluble CD14, <0.500 mg/L FEU for D-dimer, and unavailable for soluble CD163. FEU, fibrinogen-equivalent units.
Figure 3.
Figure 3.
Mean change from baseline in soluble CD14, soluble CD163, and D-dimer by week 96: A–C, virologic response; D–F, PDVF status. a Low numbers of participants in some subgroups. Data not available for week 12. b Before week 24, PDVF was defined as HIV-1 RNA ≥400 copies/mL after confirmed suppression to <400 copies/mL or an increase >1 log10 copies/mL in HIV-1 RNA above a nadir level ≥40 copies/mL. At or after week 24, PDVF was defined as HIV-1 RNA ≥400 copies/mL. Error bars represent SD. FEU, fibrinogen-equivalent units; PDVF, protocol-defined virologic failure.
Figure 4.
Figure 4.
Mean change from baseline: A, soluble CD14; B, soluble CD163; C, D-dimer by week 96 CD4+ T-cell count. Conclusions drawn from these data are limited due to low numbers of participants in some subgroups. Error bars represent SD. FEU, fibrinogen-equivalent units.
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