Integrase strand transfer inhibitors (INSTIs) such as raltegravir and dolutegravir represent a key antiretroviral drug class. They inhibit HIV replication at which specific step?

• A Prevents reverse transcriptase converting HIV RNA to proviral DNA
• B Inhibits HIV protease preventing cleavage of polyprotein into mature viral proteins
• C Blocks CCR5 co-receptor engagement preventing viral entry into CD4 T cells
• D Blocks HIV integrase from catalysing insertion (strand transfer) of proviral DNA into host chromosomal DNA ✓

Explanation

After reverse transcription, the viral integrase enzyme catalyses two steps: 3'-processing (trimming the viral DNA ends) and strand transfer (inserting the trimmed viral DNA into the host genome). INSTIs specifically block the strand transfer step by chelating the two magnesium ions in the integrase active site, preventing integration of proviral DNA. Without integration, the viral genome cannot be transcribed persistently. Reverse transcriptase is targeted by NRTIs/NNRTIs; HIV protease by lopinavir/darunavir; CCR5 by maraviroc.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.