Cost-effectiveness of lenacapavir versus tenofovir disoproxil fumarate plus emtricitabine for pre-exposure prophylaxis to prevent HIV-1 transmission in gay, bisexual, and other men who have sex with men in Spain.

BACKGROUND

Lenacapavir (LEN), a twice-yearly subcutaneous capsid inhibitor, has demonstrated superior efficacy over daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as HIV pre-exposure prophylaxis (PrEP) in clinical trials. No European cost-effectiveness analyses have been published to date. We aimed to assess the cost-effectiveness of LEN versus TDF/FTC as PrEP for gay, bisexual, and other men who have sex with men (GBMSM) in Spain.

METHODS

We developed a deterministic, compartmental HIV dynamic transmission model stratified by age (from 16 up to 100 years) and four sexual-activity risk strata, calibrated to Spanish epidemiological data (2019-2023) using Latin Hypercube Sampling (100,000 runs) with local optimisation. Outcomes included quality-adjusted life-years (QALYs) and direct costs (2023€), both discounted at 3% annually over a 20-year horizon, from the Spanish National Health System perspective. Deterministic one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA; 1000 iterations) were conducted, alongside a price-threshold analysis.

FINDINGS: In the base case, LEN PrEP generated 2983 incremental QALYs at an incremental cost of €60.68 billion compared with TDF/FTC, yielding an incremental cost-effectiveness ratio (ICER) of €20,342,776 per QALY gained. At Spain's gross domestic product per capita willingness-to-pay threshold (€33,395/QALY), the vial price would need to fall from €21,088.55 to €769.36 per semi-annual injection to be cost-effective-a 96.4% reduction. In the PSA, the ICER of the means was €11,052,594/QALY and the probability of LEN PrEP being cost-effective was 0.001.

INTERPRETATION: LEN PrEP provides meaningful health benefits compared with TDF/FTC but at a cost far exceeding the accepted Spanish willingness-to-pay threshold. At current pricing, it is not cost-effective under any scenario examined and would require an approximate 96% price reduction to become cost-effective. While LEN represents a promising long-acting HIV prevention strategy, its population-level value is currently constrained by affordability. Substantial price reductions will likely be required to enable equitable access and realise its full public health potential.

FUNDING: None.