A 35-year-old man with known HIV is tested for hepatitis C co-infection. Anti-HCV ELISA is negative. However, HCV RNA by PCR (NAAT) is positive at 850,000 IU/mL. What explains this discordant result?

• A False positive PCR from laboratory contamination; ELISA result is reliable
• B Window period of acute primary HCV infection; will seroconvert within 72 hours
• C Occult HCV infection with latent intrahepatic replication; serum PCR is always negative in this variant
• D Seronegative HCV — profoundly immunosuppressed HIV patients may not mount detectable anti-HCV IgG; RNA PCR is the gold standard in this setting ✓

Explanation

In severely immunocompromised patients, particularly those with advanced HIV disease and low CD4 counts, seronegative HCV infection is well documented: the humoral immune response to HCV antigens is insufficient to produce detectable antibody titres despite active viraemia. HCV RNA NAAT (quantitative PCR) remains positive as it detects viral nucleic acid independent of the immune response. WHO recommends HCV RNA NAAT as the preferred test for diagnosis in immunocompromised individuals and for all diagnostic confirmation. This is distinct from the acute window period, which typically resolves within 6-8 weeks of infection.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.