emtricitabine

Emtricitabine is a synthetic nucleoside analog of cytidine that inhibits HIV-1 reverse transcriptase. Mechanism: requires intracellular phosphorylation to its active triphosphate form, which competes with deoxycytidine triphosphate (dCTP) for incorporation into viral DNA by reverse transcriptase, causing chain termination due to lack of a 3'-OH group. It has activity against both HIV-1 and HIV-2, and also hepatitis B virus (HBV), though it is not FDA-approved for HBV monotherapy due to risk of resistance and viral rebound/hepatic flares upon discontinuation in HBV-coinfected patients. Clinical uses: component of combination ART regimens (commonly paired with tenofovir disoproxil fumarate or tenofovir alafenamide), and used in PrEP regimens (Truvada, Descovy) to prevent HIV acquisition in high-risk individuals. Pharmacokinetics: good oral bioavailability, long intracellular half-life allowing once-daily dosing, renally eliminated (dose adjustment needed in renal impairment). Adverse effects: generally well-tolerated; can cause hyperpigmentation (especially on palms/soles, more common in dark-skinned patients), headache, nausea, diarrhea, and rarely lactic acidosis/hepatomegaly with steatosis (class effect of NRTIs due to mitochondrial toxicity from DNA polymerase gamma inhibition). Resistance: M184V/I mutation in reverse transcriptase confers high-level resistance to emtricitabine and lamivudine (cross-resistance), but interestingly increases susceptibility to other NRTIs like tenofovir and AZT (zidovudine). Key boards points: NRTI mechanism and class effects (lactic acidosis, lipodystrophy), M184V resistance mutation significance, use in PrEP, and necessity of testing for HBV coinfection and renal function before starting therapy. Important to discontinue carefully in HBV-coinfected patients due to risk of hepatitis flare.