Clinical meaning
Antiretroviral therapy (ART) targets specific steps in the HIV lifecycle using multiple drug classes to achieve durable viral suppression. The backbone of most regimens is two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) combined with a third agent from another class. NRTIs (tenofovir, emtricitabine, abacavir, lamivudine) are nucleoside analogs that, after intracellular phosphorylation, compete with natural nucleotides for incorporation into the growing viral DNA chain by reverse transcriptase, causing chain termination. Two forms of tenofovir exist: tenofovir disoproxil fumarate (TDF — higher risk of renal and bone toxicity) and tenofovir alafenamide (TAF — less renal/bone toxicity but may worsen lipids). Integrase strand transfer inhibitors (INSTIs) — dolutegravir, bictegravir, cabotegravir — block integrase from inserting viral DNA into the host chromosome. INSTIs are now preferred third agents due to superior efficacy, high barrier to resistance (dolutegravir, bictegravir), rapid viral load decline, favorable side effect profile, and minimal drug interactions. Preferred first-line regimens include: bictegravir/TAF/emtricitabine (Biktarvy), dolutegravir + TAF/emtricitabine, or dolutegravir/lamivudine (Dovato — two-drug regimen for treatment-naive without hepatitis B, viral load <500,000, or resistance). Non-nucleoside RTIs (NNRTIs — efavirenz, rilpivirine, doravirine) bind directly to reverse transcriptase causing conformational change; older agents have low genetic barrier to resistance. Protease inhibitors (PIs — darunavir/ritonavir) block viral protease from cleaving polyproteins; boosted with ritonavir or cobicistat. Resistance testing (genotypic) is performed at diagnosis and at virologic failure (viral load >200 copies/mL on ART).