An HIV-positive patient on ART has an undetectable viral load but a CD4 count of 85 cells/μL after 3 years of therapy. He develops oral thrush and is started on fluconazole. His current regimen includes tenofovir, emtricitabine, and efavirenz. The immunological non-response (poor CD4 recovery despite viral suppression) is termed:
- A Immunological non-responder (INR) — discordant response ✓
- B Virological failure with residual low-level viral replication below standard assay detection
- C ART failure due to NRTI resistance mutation K65R in tenofovir
- D Immune reconstitution inflammatory syndrome (IRIS) involving persistent lymphopenia
Explanation
Patients who achieve virological suppression (<50 copies/mL) on ART but fail to mount adequate CD4 recovery are called immunological non-responders (INR) or immunovirological discordant responders. This occurs in 15–30% of ART-treated patients, more common with advanced baseline immunosuppression (CD4 <100), older age, and co-infections. Mechanisms include thymic insufficiency, persistent immune activation, and lymphocyte redistribution. The preferred ART response is both virological AND immunological (CD4 rising >100 cells/μL/year initially). IRIS is inflammatory worsening due to restored immunity reacting to pre-existing pathogens — it is not characterized by persistent lymphopenia with undetectable viral load.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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