What is the approved dosing regimen (loading and maintenance) for lenacapavir (Sunlenca/Yeztugo) in an adult or adolescent weighing ≥35 kg with HIV?

Lenacapavir Treatment Dosing for HIV

For adults and adolescents ≥35 kg with multidrug-resistant HIV-1, lenacapavir is initiated with oral loading doses followed by subcutaneous injections every 6 months, using one of two FDA-approved regimens. 1

FDA-Approved Dosing Regimens

Lenacapavir offers two initiation options, both leading to the same maintenance schedule 1:

Option 1: Same-Day Injection Start

• Day 1: 927 mg subcutaneous injection (2 × 1.5 mL) PLUS 600 mg oral (2 × 300 mg tablets) 1
• Day 2: 600 mg oral (2 × 300 mg tablets) 1
• Maintenance: 927 mg subcutaneous injection every 6 months (26 weeks ±2 weeks) 1

Option 2: Delayed Injection Start

• Day 1: 600 mg oral (2 × 300 mg tablets) 1
• Day 2: 600 mg oral (2 × 300 mg tablets) 1
• Day 8: 300 mg oral (1 × 300 mg tablet) 1
• Day 15: 927 mg subcutaneous injection (2 × 1.5 mL) 1
• Maintenance: 927 mg subcutaneous injection every 6 months (26 weeks ±2 weeks) 1

Administration Details

Injection technique is critical to avoid serious complications:

• Administer subcutaneously into the abdomen only by a healthcare provider 1
• Never inject intradermally due to risk of serious injection site reactions 1
• Use aseptic technique and visually inspect the yellow solution for particulates before administration 1
• Each complete dose requires two separate 1.5 mL injections 1

Missed Dose Management

Planned Missed Injections (>2 weeks late)

• If 26-28 weeks since last injection: Take 300 mg oral weekly for up to 6 months 1
• Resume maintenance injection within 7 days after the last oral dose 1

Unplanned Missed Injections (>28 weeks)

• Clinically reassess the patient, including consideration of lenacapavir resistance testing 1
• If no oral bridging was used: Reinitiate with either Option 1 or Option 2 loading regimen, then continue maintenance dosing 1
• For injection delays of 7 days or more during maintenance, oral bridging with a potent antiretroviral regimen (such as bictegravir/emtricitabine/tenofovir alafenamide) should be initiated 2

Critical Clinical Considerations

Patient selection and counseling are paramount:

• Carefully select patients who agree to the required every-6-month injection schedule 1
• Counsel patients about the importance of adherence to both scheduled injections and concomitant oral antiretroviral therapy 1
• Poor adherence to the injection schedule is a risk factor for virological failure 2

Expected virologic response:

• In clinical trials, 83% of heavily treatment-experienced patients with multidrug-resistant HIV achieved HIV-1 RNA <50 copies/mL at week 52 3
• Injection site reactions occur in 63% of participants but are typically mild to moderate and rarely lead to discontinuation 4

Monitoring requirements:

• Measure HIV RNA at 4-6 weeks after initiation to assess early response 5
• Continue monitoring every 3 months until viral suppression is achieved 5
• Standard lenacapavir monitoring includes liver enzyme tests every 6 months 6

Common Pitfalls to Avoid

• Do not administer intradermally—this significantly increases the risk of serious injection site reactions 1
• Do not use alternative injection sites—only abdominal subcutaneous administration is approved; anterior thigh injections did not reach pharmacokinetic targets 7
• Do not delay resistance testing if viral load remains elevated despite apparent adherence, as lenacapavir resistance can emerge (occurred in 9 of 72 participants in clinical trials) 3
• Do not assume adherence is adequate without thorough assessment—patients unable to attend scheduled injections require close attention and interventions to return to care 2
• Do not withhold effective antiretroviral therapy due to substance use disorders; lenacapavir's twice-yearly dosing may actually improve adherence in these populations 2