A 28-year-old man from rural Maharashtra presents to a tertiary care centre with a 3-month history of fever, weight loss, and chronic diarrhoea. On examination, he has oral candidiasis and generalized lymphadenopathy. CD4 count is 180 cells/μL. Which investigation is most appropriate to confirm HIV infection in this patient?

Explanation

## Investigation of Choice for HIV Confirmation **Key Point:** The fourth-generation antigen-antibody combination immunoassay is the recommended screening and confirmatory test for HIV in India, as per NACO (National AIDS Control Organization) guidelines and WHO recommendations. ### Why Fourth-Generation Test? **High-Yield:** Fourth-generation tests detect both HIV antibodies (IgG and IgM) AND p24 antigen simultaneously, providing: - Earlier detection (antibody + antigen detection) - Higher sensitivity during acute infection and window period - Ability to detect infection 18–45 days post-exposure (vs. 23–35 days for third-generation antibody-only tests) - Reduced window period compared to third-generation assays ### Testing Algorithm in India | Test | Use | Sensitivity | Specificity | |------|-----|-------------|-------------| | Fourth-generation Ag-Ab combo ELISA | Initial screening & confirmation | 99.8% | 99.9% | | p24 Antigen ELISA alone | Early acute infection only | 85–90% | 99% | | HIV RNA PCR | Viral load quantification, acute infection | 100% | 100% | | Western blot | Confirmatory (now rarely used in India) | 99.9% | 99.9% | **Clinical Pearl:** In this patient with CD4 <200 cells/μL and opportunistic infections (oral candidiasis, chronic diarrhoea), the diagnosis is almost certainly AIDS. However, the question asks for the INVESTIGATION OF CHOICE for confirmation, which is the fourth-generation test as per NACO algorithm. **Mnemonic:** **NACO Algorithm = NAC** → National AIDS Control Organization recommends fourth-generation Ag-Ab combo as first-line confirmatory test. ### NACO HIV Testing Algorithm ```mermaid flowchart TD A[Suspected HIV infection]:::outcome --> B[Fourth-generation Ag-Ab ELISA]:::action B --> C{Result}:::decision C -->|Positive| D[Repeat same test]:::action C -->|Negative| E[HIV negative]:::outcome D --> F{Confirmatory?}:::decision F -->|Positive| G[HIV confirmed positive]:::outcome F -->|Discordant| H[HIV RNA PCR for confirmation]:::action H --> I{RNA detected?}:::decision I -->|Yes| J[HIV positive]:::outcome I -->|No| K[HIV negative]:::outcome ``` [cite:Park 26e Ch 8]