Modelling the 5-Year Impact of Twice-Yearly Injectable Lenacapavir for HIV Pre-Exposure Prophylaxis in the United...

The impact of pre-exposure prophylaxis (PrEP) on the US HIV-1 epidemic has not been fully maximized, potentially due to challenges in uptake, coverage, adherence and consistent use. Following the FDA (Food and Drug Adminstration) approval of twice-yearly lenacapavir, epidemiological projections are needed to understand the potential role of lenacapavir in overcoming PrEP barriers. The objective of this analysis was to estimate the impact of lenacapavir on HIV-1 incidence in the United States.

We used a static cohort model representing the US population aged 15 or older to predict the number of HIV-1 cases averted between 2026 and 2030 under different lenacapavir uptake scenarios (S1-S5) versus projected status quo 2025 PrEP use with no lenacapavir (S0). In S0 and S3, we assumed 2025 levels of PrEP use (652K total PrEP users with no lenacapavir use) for 2026-2030. In all other scenarios, we assumed PrEP use increases to 1.1 million PrEP users with 0%-100% using lenacapavir. Oral and injectable PrEP effectiveness were based on clinical trials adjusted by percent days covered in real-world use. Oral PrEP use was assumed to be zero among people who inject drugs in all scenarios.

In S1, moderate lenacapavir uptake (37% of PrEP users by 2030) averted 13,700 (95% credible interval: 10,800-18,300) new HIV-1 cases, an 8% (6%-10%) reduction in cumulative cases between 2026 and 2030 relative to S0. In S2, more rapid lenacapavir uptake (85% of PrEP users by 2030) averted 23,800 (19,100-33,700) cases. Switching all PrEP users to lenacapavir averted 22,400 (12,200-47,200) and 37,400 (26,800-61,200) cases without (S3) and with (S4) an increase in PrEP use, respectively. In S5, 9400 (4600-11,500) cases were averted if PrEP use increased but lenacapavir was not introduced. This analysis was limited as only reductions in primary acquisitions were considered in the static cohort model and the model did not account for potential future demographic or behavioural shifts.

Twice-yearly lenacapavir may impact the US HIV-1 epidemic by improving adherence and increasing the duration of protection relative to oral PrEP, leading to more consistent protection over time and reducing HIV-1 incidence.