OBJECTIVES:

Lenacapavir (LEN), a first-in-class multi-stage HIV capsid inhibitor, is indicated in combination with an optimized background regimen (OBR) for the treatment of HIV-1 in heavily treatment-experienced (HTE) adults with multi-drug resistant (MDR) HIV-1 failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations. Historically, this population has had limited treatment options, leading to virologic failure and high risk of AIDS-related mortality. The health outcomes associated with LEN+OBR versus relevant comparators in this population were evaluated previously. This current analysis aimed to assess the cost-effectiveness of LEN+OBR.

METHODS:

A Markov state-transition model with a US commercial healthcare payer perspective compared LEN+OBR versus fostemsavir (FTR)+OBR and ibalizumab (IBA)+OBR. The base case model used a lifetime time horizon (70 years) and a 3.0% annual discount rate. Key inputs included transition probabilities between viral load and CD4 cell count categories, AIDS-defining events, (dis)utilities, mortality rates, healthcare resource use, drug acquisition and administration costs. Inputs were informed by literature reviews, indirect treatment comparisons, clinical opinion and internal sources (all costs in 2021/22 USD or inflated to 2021 USD using the consumer price index). Incremental cost-effectiveness ratios were generated for each pairwise comparison. Uncertainty was explored using deterministic and probabilistic sensitivity analyses (DSAs and PSAs).

RESULTS:

LEN+OBR was associated with additional quality-adjusted life years (QALYs; FTR+OBR: +0.79; IBA+OBR: +1.26) and lower costs (FTR+OBR: −$179,203; IBA+OBR: −$253,046) versus FTR+OBR and IBA+OBR and was therefore dominant. The sensitivity analyses demonstrated that results were robust to input variation, with LEN+OBR remaining below a $50,000/QALY willingness-to-pay-threshold and maintaining dominance versus FTR+OBR and IBA+OBR in all DSA, and the mean PSA, analyses.

CONCLUSIONS:

LEN+OBR dominated FTR+OBR and IBA+OBR. Therefore, LEN appears to be more favorable in terms of both costs and health outcomes compared to other available therapies when considering options for optimizing treatment for HTE adults with MDR HIV-1.