Abstract Background Fostemsavir (FTR) is a pre-attachment inhibitor that binds directly to viral gp120 preventing HIV interaction with the host immune cell. This unique mechanism may drive the robust CD4+ T-cell recovery seen in the BRIGHTE study. Here, we evaluate changes in immunologic parameters following addition of FTR to antiretroviral (ARV) regimens among virally suppressed immune non-responders (INRs) through 48 weeks. Methods RECOVER (NCT05220358) is an ongoing, open-label clinical trial that enrolled adult INRs defined as those with HIV-1 RNA50 copies/mL and CD4+ T-cell count 350 cells/mm3 while on suppressive ARVs for ≥2 years. Participants added FTR to their baseline ARV regimen and were followed for 48 weeks. Co-primary endpoints are mean and median change in CD4+ T-cell count at Week 48 using pre-FTR mean and median CD4+ T-cell counts 96 weeks prior to study entry as controls. 48-week data from the first 23 participants are included in this interim analysis. Results 22% enrolled were women, 74% were aged≥50 years and 65% were non-white. At baseline, mean duration of HIV infection, ARV therapy and viral suppression were 24.5, 24.7, and 18.4 years respectively. Baseline mean and median CD4+ T-cell counts were 248 cells/mm3 and 252 cells/mm3. At Week 48, mean and median CD4+ T-cell count significantly increased by 40 cells/mm3 and 32 cells/mm3 compared to pre-FTR controls (p=0.021 for mean and 0.024 for median). This was accompanied by an increase in mean and median CD4+ percentage of 0.5% and 0.9% compared to pre-FTR controls (p=0.372 for mean and 0.176 for median). Mean change from baseline in CD4/CD8 ratio was +0.02 (p=0.12). At Week 48, the proportion with CD4+ T-cell count≥350 cells/mm3 was 24%. Through Week 48, 2 participants had confirmed HIV-1 RNA≥50 copies/mL, however resuppressed on FTR plus the baseline ARV regimen. Drug-related adverse events (AEs) occurred in 17% and led to discontinuation in 4%. There were no drug-related serious AEs. Conclusion Data from this interim analysis demonstrates significant increases in CD4+ T-cell parameters after the addition of FTR among virally suppressed INRs through Week 48. Further studies in larger samples are needed to confirm these findings and understand the biological mechanisms which may mediate these effects. Disclosures Charlotte-Paige M. Rolle, MD, MPH, Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|MSD: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Federico Hinestrosa, MD, Gilead Sciences: Honoraria|MSD: Honoraria
Rolle et al. (2026) studied this question.