Lenacapavir (Sunlenca)
Lenacapavir is a long-acting HIV-1 capsid inhibitor initially approved for heavily treatment-experienced adults with multidrug-resistant HIV-1 (Sunlenca, CAPELLA). In 2025 it gained approval for HIV pre-exposure prophylaxis based on PURPOSE-1 and PURPOSE-2, offering twice-yearly dosing — a major shift in HIV prevention.
- Mechanism of action
- First-in-class HIV-1 capsid inhibitor that interferes with multiple stages of the viral life cycle (capsid function, nuclear import, assembly).
- Administration route
- Subcutaneous injection every 6 months, with oral loading phase.
FDA-approved indications (2026)
Multidrug-resistant HIV-1
In combination with other antiretrovirals for heavily treatment-experienced adults whose current regimen is failing due to resistance/intolerance.
HIV pre-exposure prophylaxis
At-risk adults and adolescents per 2025 label expansion (flagged: 2026 guideline incorporation continuing).
Dosing: adult, renal, and hepatic
| Population | Dose |
|---|---|
| Loading (treatment) | Day 1: 927 mg SC + 600 mg PO; Day 2: 600 mg PO; Day 8: 300 mg PO. |
| Maintenance (treatment) | 927 mg SC every 26 weeks. |
| PrEP (per 2025 label) | Loading regimen followed by 927 mg SC every 26 weeks (flagged: confirm current label schedule). |
| Renal impairment | No dose adjustment in mild-moderate; limited data in severe renal impairment. |
| Hepatic impairment | No dose adjustment in mild-moderate; not studied in severe. |
Contraindications and boxed warnings
Contraindications
- Concomitant strong CYP3A/P-gp/UGT1A1 inducers (e.g., rifampin, carbamazepine, phenytoin, St John's wort).
2026 guideline and pivotal trial position
2026 DHHS HIV treatment guidelines recommend lenacapavir + an optimized background regimen for treatment-experienced, MDR-HIV adults. For PrEP, 2026 CDC guidance integrates twice-yearly subcutaneous lenacapavir as an option alongside oral TDF/TAF-based PrEP and long-acting cabotegravir, with emphasis on implementation logistics (cold chain, SC infrastructure, follow-up HIV testing).
CAPELLA
Sustained viral suppression in heavily treatment-experienced adults with MDR HIV-1.
PURPOSE-1
100% prevention of HIV acquisition in cisgender women at risk, compared with background oral PrEP.
PURPOSE-2
Superior HIV prevention vs daily oral PrEP in MSM, transgender, and gender-nonconforming individuals.
Cross-system reasoning
Lenacapavir's twice-yearly subcutaneous dosing brings HIV prevention into the same infrastructure conversation as long-acting contraception, intramuscular neuroleptics, and depot oncology therapies. It intersects with primary care (adherence reality, rural access), infectious disease (resistance monitoring), and pharmacy (cold chain and scheduled injection workflows). Drug interactions with tuberculosis therapy must be screened before initiation.
Key references
Related clinical reading
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This reference is for US-licensed physicians and is not a substitute for the full FDA prescribing information. Dosing in special populations, drug interactions, and emerging safety information should be verified against the current manufacturer label and society guidelines before prescribing.