Lenacapavir, the first long-acting injectable antiretroviral given every 6 months, inhibits HIV replication at multiple stages by targeting which HIV protein?
- A HIV integrase strand transfer — blocking viral DNA integration into host chromatin
- B HIV capsid protein (CA, p24) — inhibiting capsid assembly, nuclear pore import, and capsid disassembly ✓
- C HIV protease — preventing Gag-Pol polyprotein cleavage and virion maturation
- D HIV reverse transcriptase — non-nucleoside inhibitor binding the polymerase domain
Explanation
Lenacapavir (GS-6207) is a first-in-class HIV capsid inhibitor. The HIV capsid (CA, p24) plays multiple essential roles: it protects the viral genome during reverse transcription, interacts with nuclear pore complex proteins (Nup153, Nup358) to facilitate nuclear import of the pre-integration complex, and undergoes controlled disassembly to release viral DNA at the nucleus. Lenacapavir interferes with all these stages by binding a conserved interface between CA subunits (the CPSF6-binding pocket). Its extremely long half-life enables twice-yearly subcutaneous injection. It is active against HIV-1 strains resistant to all other drug classes and has no known pre-existing resistance. Integrase inhibitors (dolutegravir), protease inhibitors, and NNRTIs target different enzymes.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.