Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV

Combination antiretroviral therapy (cART) blocks intracellular human immunodeficiency virus (HIV) replication in CD4+ T-lymphocytes, but fails to eliminate latent HIV infected CD4+ T-lymphocytes. About 7 (range \<1-100) in 106 of these cells are latently infected and can cause reactivation of proviral HIV when cART is stopped. These latently infected cells form the reservoir and must be targeted in order to cure HIV. We would like to further investigate this reservoir and assess potential interventions to eradicate it. One promising option is to further study the influence of HIV latency disruptors (latency reversing agents, LRA) on the HIV infected reservoir. These agents are used in shock and kill strategies that disrupt latency by LRA followed by the selective (induced) killing of the reservoir cell due to viro-pathogenic effects. For accurate assessment of the reservoir and potential cure strategies, including the impact of LRA on the reservoir, a large reservoir and sufficient cells for analysis are desirable. Our understanding on the reservoir comes from in vitro lymphocyte models and early ex vivo studies. Additional studies of patients with different clinical phenotypes including untreated versus treated versus the rare individuals that control HIV spontaneously are increasingly relevant to the field. Especially this last category represent biological examples of viral control without cART and are useful to study the factors that set them apart from those that need t…

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Casper Rokx, MD PhD  ·  c.rokx@erasmusmc.nl

Rob Gruters, PhD  ·  r.gruters@erasmusmc.nl

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