A 28-year-old woman with newly diagnosed HIV infection (CD4 count 350 cells/μL, viral load 150,000 copies/mL) is asymptomatic. She is counseled about antiretroviral therapy (ART) initiation. Before starting ART, which investigation is most appropriate to guide drug selection and assess for drug interactions?

Explanation

## Pre-ART Baseline Investigations: Genotypic Resistance Testing ### Clinical Context The patient is newly diagnosed with HIV and has not received prior ART. Before initiating therapy, baseline genotypic resistance testing is essential to: 1. Identify pre-existing drug-resistant mutations 2. Guide selection of an effective regimen 3. Prevent treatment failure from the outset ### Comparison of Pre-ART Investigations | Investigation | Purpose | Timing | Clinical Use | |---|---|---|---| | **Genotypic resistance testing** | Identify drug-resistant mutations | Before ART initiation | **Guide drug selection** | | **CD4 count** | Assess immunosuppression severity | Baseline & ongoing | Determine OI prophylaxis, prognosis | | **Viral load (RNA)** | Quantify viral replication | Baseline & ongoing | Assess disease activity, treatment response | | **HLA-B*5701 testing** | Screen for abacavir hypersensitivity | Before abacavir use | Prevent severe HSR reaction | **Key Point:** Genotypic resistance testing is recommended for ALL newly diagnosed patients before ART initiation, regardless of prior treatment history, because transmitted drug resistance (TDR) is common in many regions. ### Why Genotypic Testing is the Answer - **Identifies pre-existing mutations** that confer resistance to NRTIs, NNRTIs, PIs, or INSTIs - **Prevents treatment failure** by avoiding drugs to which the virus is already resistant - **Improves first-line regimen efficacy** — allows selection of drugs with genetic barrier to resistance - **Standard of care** — recommended by WHO, CDC, and Indian National AIDS Control Organization (NACO) **High-Yield:** In resource-limited settings where genotypic testing is unavailable, empiric first-line regimens (e.g., TDF/FTC/EFV or TDF/FTC/DTG) are used; however, genotypic testing remains the gold standard when available. **Clinical Pearl:** Transmitted drug resistance (TDR) prevalence in India is ~5–10%, making baseline resistance testing especially important in newly diagnosed patients. [cite:Harrison 21e Ch 197]