Co-receptor usage by HIV-1 determines cell tropism. Macrophage-tropic (M-tropic, R5) HIV strains use CCR5 as the co-receptor. The natural resistance of homozygous CCR5-Δ32 mutation (deletion of 32 bp) individuals to HIV infection inspired which therapeutic drug?

• A Enfuvirtide (T-20) — fusion inhibitor
• B Tenofovir — nucleotide reverse transcriptase inhibitor
• C Maraviroc — CCR5 antagonist (entry inhibitor) ✓
• D Raltegravir — integrase strand transfer inhibitor

Explanation

Individuals homozygous for the CCR5-Δ32 deletion lack cell-surface CCR5 expression and are highly resistant to R5-tropic HIV infection. This observation led to the development of maraviroc (a small-molecule CCR5 antagonist), which blocks the CCR5 co-receptor, preventing viral entry. Before initiating maraviroc, a tropism test (Trofile assay or genotypic tropism testing) must confirm R5-only virus, as maraviroc is ineffective against X4-tropic or dual-mixed HIV strains. The Berlin Patient cure also exploited this principle using a CCR5-Δ32 donor for HSCT.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.