Which antiretroviral drug class acts by inhibiting the reverse transcriptase enzyme and is most commonly associated with peripheral neuropathy as a dose-limiting toxicity?

Explanation

## Nucleoside Reverse Transcriptase Inhibitors (NRTIs) **Key Point:** NRTIs are nucleoside analogues that inhibit HIV reverse transcriptase by chain termination. They are incorporated into the growing DNA strand during reverse transcription, causing premature chain termination and blocking viral replication. ### Mechanism of Action 1. Compete with natural nucleosides (dNTPs) for incorporation into viral DNA 2. Lack a 3'-OH group, preventing phosphodiester bond formation 3. Result in chain termination and prevention of viral DNA synthesis ### Toxicity Profile | NRTI | Dose-Limiting Toxicity | Other Notable AEs | |------|------------------------|-------------------| | **Didanosine (ddI)** | Peripheral neuropathy, pancreatitis | Lactic acidosis | | **Zalcitabine (ddC)** | Peripheral neuropathy | Oral ulcers, pancreatitis | | **Stavudine (d4T)** | Peripheral neuropathy, lipodystrophy | Lactic acidosis, pancreatitis | | **Zidovudine (AZT)** | Bone marrow suppression | Myopathy, lactic acidosis | | **Lamivudine (3TC)** | Minimal toxicity | Hepatitis flare (HBV co-infection) | | **Abacavir (ABC)** | Hypersensitivity reaction | Lactic acidosis | **High-Yield:** Peripheral neuropathy is the hallmark dose-limiting toxicity of didanosine, zalcitabine, and stavudine — the older NRTIs. This is a classic NEET PG question. **Clinical Pearl:** Modern ART regimens have largely replaced these neurotoxic NRTIs with newer agents (tenofovir, emtricitabine) that have better tolerability profiles. **Mnemonic:** **"DDS"** — **D**idanosine, **d**C (zalcitabine), **d4T** (stavudine) = the "neuropathy trio" of NRTIs.