A 32-year-old man with newly diagnosed HIV infection (CD4 count 450 cells/μL, viral load 95,000 copies/mL) is being evaluated for antiretroviral therapy initiation. Before starting therapy, which investigation is most appropriate to guide selection of the NNRTI-based or PI-based regimen?

Explanation

## Rationale for HIV Genotype Resistance Testing **Key Point:** HIV genotype resistance testing is the gold standard investigation for detecting mutations conferring resistance to NRTIs, NNRTIs, and PIs before initiating first-line ART. ### Why Genotype Testing? Genotype testing identifies specific mutations in reverse transcriptase and protease genes that confer resistance to antiretroviral drugs. This information directly guides selection between NNRTI-based (e.g., efavirenz, rilpivirine) and PI-based (e.g., lopinavir/ritonavir) regimens, ensuring the chosen backbone is active against the patient's viral strain. ### Clinical Application 1. Detects NNRTI resistance mutations (K103N, Y181C) → avoid NNRTIs 2. Detects PI resistance mutations (L90M, V82A) → avoid or modify PI choice 3. Guides optimal first-line regimen selection 4. Prevents treatment failure and emergence of additional resistance **High-Yield:** Genotype testing should be performed **before ART initiation** in all treatment-naïve patients, especially in resource-limited settings with high transmitted drug resistance (TDR) prevalence. ### Comparison with Other Investigations | Investigation | Timing | Purpose | Guides ART Selection? | |---|---|---|---| | **Genotype resistance** | Before ART start | Detect existing mutations | YES — directly | | CD4/VL | Before ART start | Assess immune status, viral burden | NO — only timing | | HLA-B*5701 | Before ART start | Screen for abacavir hypersensitivity | NO — NRTI toxicity only | | Tropism assay | Before maraviroc use | Determine CCR5/CXCR4 tropism | NO — only for CCR5 antagonists | **Clinical Pearl:** In India, transmitted drug resistance (TDR) rates to NNRTIs are rising (10–15% in some cohorts), making baseline genotyping increasingly critical for treatment success [cite:WHO 2019 ART Guidelines].