## Salvage Therapy for Lamivudine-Resistant HBV **Key Point:** Tenofovir monotherapy is the preferred salvage agent for lamivudine-resistant HBV. It is active against YMDD mutants and has a high genetic barrier to further resistance. ## Resistance Patterns and Management | Agent | Resistance Mechanism | Cross-resistance to Lamivudine | Salvage Option | |-------|---------------------|-------------------------------|----------------| | **Lamivudine** | YMDD mutations (M204V/I) | — | Yes | | **Entecavir** | rtT184G, rtS202I, rtM250V | Partial (if YMDD present) | Limited | | **Tenofovir** | Rare (<1%) | No cross-resistance | **Preferred** | | **Adefovir** | rtA181T, rtN236T | No cross-resistance | Alternative | **High-Yield:** Tenofovir is a nucleotide analog that does NOT share cross-resistance with lamivudine-resistant strains (YMDD mutants). It is the WHO and AASLD-recommended salvage agent for lamivudine resistance. **Clinical Pearl:** In lamivudine-resistant patients, monotherapy with a high-barrier agent (tenofovir or adefovir) is preferred over combination therapy. Tenofovir is superior to adefovir due to better potency and lower resistance emergence rate. **Warning:** Entecavir monotherapy in lamivudine-resistant patients carries a risk of entecavir resistance emergence (rtT184G, rtS202I). While entecavir has intrinsic potency, it is NOT recommended as monotherapy for lamivudine-resistant disease — always use tenofovir or adefovir. ## Salvage Therapy Algorithm for Lamivudine Resistance ```mermaid flowchart TD A[Lamivudine-resistant HBV confirmed]:::outcome --> B{Entecavir-naive?}:::decision B -->|Yes| C[Tenofovir monotherapy]:::action B -->|No, prior entecavir exposure| D[Adefovir monotherapy]:::action C --> E[Monitor HBV DNA & resistance]:::action D --> E F[Do NOT use entecavir monotherapy]:::urgent ``` [cite:Harrison 21e Ch 297]
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