(345) Cost-Effectiveness Analysis of Lenacapavir Compared to Cabotegravir and Generic Oral FTC/TDF for HIV Pre-Exposure Prophylaxis among Cis-gender Women in the United States

Background: : Lenacapavir (LEN-LA) is a bi-annual injectable HIV Pre-exposure Prophylaxis (PrEP) drug which has shown promising results in clinical trials among cis-gender women in terms of HIV prevention.

Objective: : This study modelled the lifetime cost-effectiveness of LEN-LA compared to the bi-monthly injectable cabotegravir (CAB-LA) and the daily oral generic emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) from a US Payer Perspective.

Methods: : A four-state Markov model simulated PrEP initiation with CAB-LA, LEN-LA, or FTC/TDF in eligible adults over a 40-year time horizon, with health states including uninfected on PrEP, uninfected off PrEP, HIV-infected, and dead. Individuals could continue initial PrEP or discontinue. Efficacy data were drawn from the HPTN 083/084 trials for CAB-LA, FTC/TDF and the PURPOSE 1 trial for LEN-LA. Additional model inputs were obtained from published literature. Lifetime HIV-related costs, transmissions, and resistance risks were modeled. The primary outcomes included incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years (QALY) at a willingness-to-pay threshold (WTP) of $100,000. All outcomes were discounted at 3%. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model.

Results: : In our model, all three PrEP strategies demonstrated comparable HIV prevention effectiveness. Both CAB-LA and LEN-LA reduced QALY losses versus FTC/TDF, with incremental lifetime costs of $54,980.72 and $60,501.75 per person, respectively. oral FTC/TDF remained the most cost-effective option. Among injectables, LEN-LA was more cost-effective than CAB-LA, with an ICER of $49,971 per QALY gained. Compared to oral FTC/TDF, LEN-LA’s ICER was $384,572 per QALY exceeding WTP. While LEN-LA offers better value among long-acting options, both injectable strategies were not cost-effective compared to oral FTC/TDF. Results were robust across sensitivity analyses. One-way sensitivity analyses identified drug costs and HIV care costs as key drivers of the ICER for LEN-LA vs. CAB-LA, while persistence on PrEP was most influential in comparisons between LEN-LA and FTC/TDF.

Conclusions: : While LEN-LA is more cost-effective than CAB-LA, its high cost renders it less cost-effective than daily oral FTC/TDF at current pricing. LEN-LA may be a viable long-acting option for populations with poor adherence to oral PrEP, but broad adoption may not be economically justified without price reductions. These findings inform value-based decision-making in formulary design to ensure patient-centered and equitable PrEP access.

Sponsorship:: None