HIV replication cycle blockade

Category: catabolism

Overview

HIV-1 replication targets beyond NRTIs (covered separately): NNRTIs bind RT in a non-competitive pocket → allosteric inhibition; INSTIs (raltegravir, dolutegravir, bictegravir, elvitegravir) inhibit integrase strand-transfer → block proviral DNA integration into host chromosome (the irreversible step); PIs (atazanavir, darunavir, lopinavir) inhibit HIV protease → immature noninfectious virions. Modern ART regimens combine 2 NRTIs + 1 anchor (INSTI preferred for safety; alternatively NNRTI or boosted PI). Cobicistat or ritonavir serve as PK boosters (CYP3A4 inhibition raises companion drug exposure — covered in CV/AM-as-perpetrator pathways).

Organ Systems

Pathway Steps

  1. hiv-rna → hiv-dna — via reverse transcriptase — NRTI/NNRTI target. HIV is a retrovirus: its reverse transcriptase copies the viral RNA genome into DNA — a step with no host equivalent, making it a prime drug target. Nucleoside (NRTI) and non-nucleoside (NNRTI) reverse-transcriptase inhibitors block this conversion, the backbone of antiretroviral therapy.
  2. hiv-dna → proviral-integration — via integrase strand-transfer — INSTI target. The viral DNA is spliced into the host genome by integrase, establishing a permanent provirus (and the latent reservoir that prevents cure). Integrase strand-transfer inhibitors (dolutegravir, bictegravir) block this step and are now first-line for their potency and high barrier to resistance.
  3. hiv-polyprotein → mature-virion — via HIV protease cleaves Gag + Gag-Pol polyproteins — PI target. New viral polyproteins must be cleaved by HIV protease into functional proteins to form an infectious, mature virion. Protease inhibitors block this maturation, yielding non-infectious particles — a third target class that, combined with the others, drives viral load below detection in modern triple therapy.

Known Modulators

References