P-533. CD4 T-cell, CD4/CD8 Ratio Improvement and a General Reduction in Inflammatory Biomarkers with Low-Level Viremia (LLV) up to Week 192 with Fostemsavir (FTR)-Based Regimens in Individuals with Multidrug-Resistant (MDR) HIV-1
Authors: Spagnuolo Vincenzo , Gregori Natalia , Marcon Iacopo , Du Fangfang , Li Bo , Wang Marcia , Dyson Alftan , Prakash Manyu , Clark Andrew 
Published: January 2025

Background

Persistent LLV (40-1000 c/mL) is associated with virologic failure, drug resistance and increased risk of inflammation and may impact morbidity and mortality. FTR (prodrug of the first-in-class attachment inhibitor temsavir) is indicated with other antiretrovirals (ARVs) for heavily treatment-experienced individuals with MDR HIV-1 unable to construct suppressive regimens. BRIGHTE participants (pts) did not have to stop FTR due to LLV. We describe outcomes and inflammatory biomarkers through Week 192 in pts with LLV (&lt; 40, 40-400, 400-1000 and &gt; 1000 c/mL) on FTR-based regimens from the Randomized Cohort (RC) in the BRIGHTE study.

Methods

BRIGHTE was a phase 3 study (N=371; RC, n=272; Non-randomized Cohort, n=99) in adults failing their current ARV regimen (HIV-1 RNA &gt; 400 c/mL) with ≤ 2 fully active approved ARVs. Pts with 1 or 2 active ARVs entered the RC and received open-label FTR + optimized background therapy after an 8-day blinded placebo-controlled period. Virologic and immunologic responses were analyzed by baseline (BL) demographics and disease characteristics.

Results

At BL in the RC, 89% of pts had CD4 T-cell count &lt; 350 cells/mm3, with 5% between 350 and &lt; 500 cells/mm3 and 6% ≥ 500 cells/mm3. Mean CD4 T-cell increase observed in the &lt; 40 c/mL (n=142) group was 331 cells/mm3, 40-400 c/mL (n=25) was 263 cells/mm3, 400-1000 c/mL (n=2) was 218 cells/mm3, and in pts with &gt; 1000 c/mL (n=10) was 107 cells/mm3. Similar mean increase in CD4/CD8 ratio was observed in pts with LLV; ratio in the &lt; 40 c/mL (n= 142) group was 0.38, 40-400 c/mL (n=25) was 0.31, 400-1000 c/mL (n=2) was 0.32, and in pts with &gt; 1000 c/mL (n=10) was 0.09. Biomarkers showed a mean general reduction; &lt; 40 c/mL (sCD14: −371 µg/L, n=133; sCD163: −134 µg/L, n=40; D-dimer: 0.16 mg/L, n=139), 40-400 c/mL (sCD14: −428 µg/L, n=21; sCD163: −80 µg/L, n=5; D-dimer: −0.14 mg/L, n=22), 400-1000 c/mL (sCD14: 1174 µg/L, n=2; sCD163: no data; D-dimer: 0.04 mg/L, n=2), &gt; 1000 c/mL (sCD14: 271 µg/L, n=10; sCD163: 107 µg/L, n=3; D-dimer: 0.08 mg/L, n=10).

Conclusion

In pts with LLV, there is a persistent increase in CD4 T-cell count and improvement in CD4/CD8 ratio, with a general reduction in inflammatory markers up to Week 192. Results highlight the value of FTR-based regimens for sustained improvement where there is incomplete virologic suppression.

Disclosures

Vincenzo Spagnuolo, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|MSD: Honoraria|ViiV Healthcare: Honoraria Natalia Gregori, MD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Iacopo Marcon, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Fangfang Du, MS in Statistics, GSK: Employee|GSK: Stocks/Bonds (Public Company) Bo Li, PhD, GSK: Employee Marcia Wang, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Alftan Dyson, PharmD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Manyu Prakash, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Andrew Clark, MD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee