Lars Jørgen Østergaard

Histone Deacetylase Inhibitor Romidepsin Inhibits de novo HIV-1 Infections

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Adjunct therapy with the histone deacetylase inhibitor (HDACi) romidepsin increases plasma viremia in HIV patients on combination antiretroviral therapy (cART). However, a potential concern is that reversing HIV latency with an HDACi may reactivate the virus in anatomical compartments with sub-optimal cART concentrations leading to de novo infection of susceptible cells in these sites. We tested physiologically relevant romidepsin concentrations known to reactivate latent HIV in order to definitively address this concern. We found that romidepsin significantly inhibited HIV infection in PBMCs and CD4+ T cells, but not in monocyte-derived-macrophages. In addition, romidepsin impaired HIV spreading in CD4+ T cell cultures. When we evaluated the impact of romidepsin on quantitative viral outgrowth assays with primary resting CD4+ T cells, we found that resting CD4+ T cells exposed to romidepsin exhibited reduced proliferation and viability. This significantly lowered assay sensitivity when measuring the efficacy of romidepsin as an HIV latency reversal agent. All together our data indicate that romidepsin-based HIV eradication strategies are unlikely to reseed a latent T cell reservoir, even under sub-optimal cART conditions, because romidepsin profoundly restricts de novo HIV infections.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Pages (from-to)3984-3994
Number of pages11
Publication statusPublished - 2015

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