Comparison: NRTIs vs NNRTIs – Anti HIV Drugs
Comparison: NRTIs vs NNRTIs
| Feature | NRTIs (Nucleoside Reverse Transcriptase Inhibitors) | NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) |
|---|---|---|
| Mechanism of Action | Act as false nucleosides; incorporated into viral DNA, causing chain termination | Bind directly to reverse transcriptase and inhibit its activity allosterically |
| Site of Action | Active site of HIV reverse transcriptase (after intracellular phosphorylation) | Allosteric site of reverse transcriptase (no phosphorylation needed) |
| Activation Requirement | Requires intracellular phosphorylation to become active | No activation required |
| Examples | Zidovudine, Lamivudine, Tenofovir, Emtricitabine | Efavirenz, Nevirapine, Delavirdine, Etravirine |
| Resistance | Slower to develop (requires multiple mutations) | Resistance develops rapidly with a single mutation |
| Drug Interactions | Fewer CYP450 interactions | Significant CYP450 interactions (esp. CYP3A4) |
| Toxicities | Lactic acidosis, hepatic steatosis, lipodystrophy | Rash, hepatotoxicity, CNS symptoms (especially with Efavirenz) |
| Role in ART Regimen | Backbone of most first-line regimens (2 NRTIs + 1 other drug) | Often the third drug in initial ART regimens (especially in low-resource settings) |
| Pregnancy Category (some) | Zidovudine is safe in pregnancy | Efavirenz contraindicated in 1st trimester (neural tube defects risk) |