Can low‐cost oral alternatives be used in place of oral Lenacapavir when initiating long‐acting lenacapavir PrEP in low‐ and middle‐income countries

LB-#1 Background: Lenacapavir (LEN) was approved by FDA June 2025 as 6-monthly subcutaneous (SC) PrEP. Since LEN takes time to reach protective plasma concentrations following injection, two options are available for initiating long-acting LEN PrEP. Option 1: 600 mg oral LEN on Days 1 and 2, with 927 mg of SC LEN also given on Day 1. Option 2: (as studied in RCTs) 600 mg of oral LEN on Days 1 and 2, followed by 300 mg oral LEN on Day 8, with 927 mg of long-acting LEN on Day 15. The need for oral LEN when initiating long-acting LEN PrEP poses significant challenges to rapid adoption in low- and middle-income countries (LMIC). Generic manufacturers would need to develop and gain approval for two new products rather than one (oral and injectable). Small market size for the oral product constitutes a barrier for manufacturers, and a fiscal challenge for LMIC healthcare providers is also anticipated, particularly when multiple low-cost oral options are already available. The current work analysed publicly available LEN pharmacokinetics with and without oral LEN at initiation to estimate how long oral PrEP with a low-cost alternative would need to be given while long-acting LEN reached protective levels. Materials and methods: LEN plasma pharmacokinetic (PK) data were available for both current initiation options (Option 1: n = 31; Option 2: n = 14)1. PK data following a single SC dose of 927 mg (dosed as 2 × 1.5 mL injections) without oral LEN in healthy volunteers was also available (n = 8)2. Plasma concentrations and measures of spread (confidence interval areas, error bars) were digitized using GetData Graph Digitizer3.