What is the recommended use and dosing regimen for Lenacapavir (HIV-1 capsid inhibitor) in the treatment of HIV-1 infection?

From the Guidelines

Lenacapavir is recommended for the prevention of HIV infection for all routes of sexual exposure, with a dosing regimen that includes an initial subcutaneous injection overlapped with 2 daily oral doses of lenacapavir (600 mg). The use of lenacapavir as an every-6-month subcutaneous injection has been shown to significantly reduce HIV incidence, with a 96% reduction in HIV incidence observed in the PURPOSE-2 trial 1. The recommended regimen begins with an initial oral loading dose, followed by a subcutaneous injection, and then maintenance therapy with subcutaneous injections every six months.

• Key points to consider when prescribing lenacapavir include:
  • The importance of using lenacapavir in combination with other antiretroviral medications as part of an optimized background regimen
  • Monitoring patients for injection site reactions, which are common but typically mild to moderate
  • Carefully evaluating drug interactions, particularly with strong CYP3A inducers or P-gp inducers which may reduce lenacapavir effectiveness
• The novel mechanism of action of lenacapavir, which inhibits HIV-1 capsid protein, makes it effective against HIV strains resistant to other antiretroviral classes, as noted in the 2024 recommendations of the international antiviral society-usa panel 1.
• Ongoing trials are investigating the use of lenacapavir for PrEP in other populations, but current evidence supports its use for prevention of HIV infection for all routes of sexual exposure 1.

From the FDA Drug Label

Table 7 Lenacapavir Exposures Following Oral and Subcutaneous Administration of SUNLENCA in Heavily Treatment Experienced Participants with HIV Parameter Mean (%CV) Recommended Dosing Regimen, Option 1 * Recommended Dosing Regimen, Option 2 * Day 1: 600 mg (oral) + 927 mg (SC) Day 2: 600 mg (oral) Days 1 and 2: 600 mg (oral), Day 8: 300 mg (oral), Day 15: 927 mg (SC)

The recommended use and dosing regimen for Lenacapavir in the treatment of HIV-1 infection is as follows:

• Option 1: Day 1: 600 mg (oral) + 927 mg (SC), Day 2: 600 mg (oral)
• Option 2: Days 1 and 2: 600 mg (oral), Day 8: 300 mg (oral), Day 15: 927 mg (SC) 2

From the Research

Recommended Use of Lenacapavir

• Lenacapavir is a long-acting subcutaneous injectable used for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistance for whom the current antiretroviral regimen is failing due to resistance, intolerance, or safety considerations 3.
• It is the first in a new class of drugs called capsid inhibitors to receive FDA approval 3.
• Lenacapavir is indicated, in combination with other antiretroviral therapy, for treatment of multidrug-resistant HIV-1 infection 3, 4.

Dosing Regimen

• The recommended dosing regimen for lenacapavir is a subcutaneous injection every 6 months 3.
• Following a 2-week oral lenacapavir loading phase, participants received subcutaneous lenacapavir every 26 weeks with an optimized background regimen (OBR) 5.
• The pharmacokinetics of lenacapavir support the use of approved lenacapavir dosing regimen in patients with mild or moderate hepatic impairment as well as in patients with mild, moderate, and severe renal impairment 6.

Efficacy and Safety

• Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks 5.
• The most common adverse events reported in the clinical trial were injection site reactions, occurring in 63% of participants 3.
• Lenacapavir was considered generally safe and well tolerated in studies evaluating its pharmacokinetics in participants with hepatic or renal impairment 6, 7.