Purpose: To describe the efficacy and durability of fostemsavir (FTR), ibalizumab (IBA) or lenacapavir (LEN)-including regimens in people living with 4-drug class resistant HIV (4DR-PLWH) in a real-life setting.

Methods: We included 4DR-PLWH from the PRESTIGIO Registry, treated with a FTR-, IBA- or LEN-including regimen and with a documented resistance to NRTIs/NNRTIs/PIs/INSTIs.

Discontinuation of FTR, IBA or LEN was defined as interruption of the drug for any cause. Follow-up (FU) started from the date of FTR, LEN or IBA start (baseline; BL) until discontinuation of FTR/IBA/LEN or death/freezing date (30/June/2023). Descriptions by median (IQR) or frequency (%). Genotypic susceptibility score for the optimized background therapy introduced with FTR/LEN/IBA was estimated according to the cumulative data of the available plasma genotyping resistance tests recorded for each patient.

Results: Among 35 4DR-PLWH, we considered 27, 11 and 10 FTR-, IBA- and LEN-including regimens, respectively (Table 1).
FTR-including regimens: at the end of FU [median duration 18.7 (5.6-82.7) months], virological efficacy (VE; HIV-RNA <200 copies/mL) was 66.7% (18/27); 8/27 (29.6%) regimens had been discontinued. Among those still in a FTR-including regimen, the median change in CD4+ was +97 (-38/+182) cells/mm³(p=0.064).
IBA-including regimens: median FU 14.1 (5.6 -39.1) months, VE was 63.6% (7/11); 4/11 (36%) regimens had been discontinued. Median CD4+ change, in those still on treatment with IBA, was +63 (-38/+122) cells/mm³(p=0.109).
LEN including regimens: median FU 30.3 (18.7-33.5) months, VE was 90% (9/10); 2/10 (20%) regimens had been discontinued. Median CD4+ change was +5 (-48/+101) cells/mm³(p=0.742).
Regimens including a concomitant administration of FTR, IBA or LEN (n=4) are described in Table 2.

Conclusions: In 4DR-PLWH, the overall efficacy and durability of FTR, IBA or LEN-including regimens were good. Efficacy and safety data on combination regimens including entry and capsid inhibitors are urgently needed in this fragile population.