In HIV management, integrase strand transfer inhibitors (INSTIs) like dolutegravir are preferred as first-line agents over efavirenz (NNRTI). The specific enzymatic step inhibited by INSTIs is:

• A Inhibition of the strand transfer step of integration — chelation of the two magnesium ions in the integrase active site, blocking insertion of processed viral DNA 3' ends into host chromosomal DNA ✓
• B Inhibition of viral integrase during 3'-processing — the initial cut at the 3' end of viral DNA ends removing dinucleotides
• C Blocking nuclear import of the pre-integration complex by binding the integrase NLS (nuclear localisation signal)
• D Preventing covalent circularisation of viral DNA via 2-LTR circle formation in the nucleus

Explanation

HIV integrase performs two enzymatic steps: (1) 3'-processing — in the cytoplasm, integrase cleaves two nucleotides from each 3' end of the viral DNA; and (2) strand transfer — in the nucleus, the processed 3' ends are inserted into host DNA. INSTIs specifically inhibit the strand transfer step by coordinating to the two Mg2+ cations in the integrase DDE motif active site, preventing the metal-dependent DNA insertion. They do not significantly inhibit 3'-processing (early step) or nuclear import. This specific inhibition of strand transfer is reflected in the class name 'integrase strand transfer inhibitors'. Cabotegravir and bictegravir are newer INSTIs with high genetic barriers to resistance.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.