Objective: Achieving virologic suppression is particularly challenging for people with HIV (PWH) who are heavily treatment-experienced with multi-drug resistance (MDR). Lenacapavir (LEN), a first-in-class multi-stage HIV capsid inhibitor, in combination with an optimized background regimen (OBR), is under investigation for treating PWH with MDR failing current therapy due to resistance, intolerance, or safety considerations. The aim of this analysis was to explore the costs and benefits of LEN+OBR versus relevant comparators in this population.

Methods: A Markov state-transition model with a US healthcare payer perspective and lifetime time horizon compared LEN+OBR versus fostemsavir (FTR)+OBR and ibalizumab (IBA)+OBR. Key model inputs included change in viral load and CD4 cell count, AIDS-defining events, (dis)utilities, mortality rates, healthcare resource use and drug acquisition costs. Inputs were informed by systematic and targeted reviews, indirect treatment comparisons, discussion with clinical experts and internal sources. Several clinical outputs were generated from the model, including undiscounted total virologically suppressed life-years (LYs) and AIDS-free LYs. Virologic suppression was defined as <50 viral copies/mL and AIDS as CD4 cell count <200 cells/mm³. Cost-effectiveness threshold analyses were also performed to assess the discounted (3% annually) incremental cost per quality-adjusted LY (QALY) gained with a range of potential LEN drug acquisition costs. Uncertainty was explored using deterministic and probabilistic sensitivity analyses.

Results: LEN+OBR was estimated to extend LYs spent virologically suppressed (LEN+OBR: 4.74; FTR+OBR: 2.73; IBA+OBR: 1.59) and increase LYs spent AIDS-free (LEN+OBR: 15.21; FTR+OBR: 13.47; IBA+OBR: 12.13) in PWH with MDR. QALYs accrued were higher for LEN+OBR as well (LEN+OBR: 13.89; FTR+OBR: 12.53; IBA+OBR: 11.47). LEN+OBR was also found to be cost-effective versus relevant comparators at a range of willingness-to-pay thresholds and prices.

Conclusion: Overall, the model results indicate that LEN+OBR is cost-effective from a US payer perspective with improved long-term clinical benefits for PWH with MDR.