Selective Elimination of HIV-1-Infected Macrophages by Targeted Activator of Cell Kill

Pyr01 selectively eliminates HIV-1-infected primary human monocyte-derived macrophages with an EC50 of ~0.36 μM, while the inactive analog Pyr02 shows minimal activity.

• Why it matters: HIV-1-infected macrophages resist many killing strategies used for CD4+ T-cell reservoirs, so reservoir-specific clearance approaches are needed for cure efforts.
• What they did: Primary human monocyte-derived macrophages were treated with Pyr01 or Pyr02, and effects on uninfected viability, extracellular virion-associated HIV-1 RNA, cell-associated viral RNA, and infected-cell loss were measured.
• The result: Pyr01 rapidly and sustainably reduced extracellular virion-associated HIV-1 RNA and decreased cell-associated viral RNA, and live-cell imaging showed marked loss of infected macrophages, supporting premature viral protease activation as a macrophage-clearance strategy.

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