Single Cell Analysis of HIV Replication Capacity and Drug Resistance

This invention provides an assay to simultaneously analyze residual susceptibility and reduced replication capacity of drug-resistant viruses which may provide the ability to make more rational therapeutic deciaions in the setting of treatment failure. HIV-1-infected individuals who develop drug-resistant virus during antiretroviral therapy may derive benefit from continued treatment for two reasons: First, drug-resistant viruses can retain partial susceptibility to the drug combination. Second, therapy selects for drug-resistant viruses that may have reduced replication capacity relative to archived, drug-sensitive viruses. JHU researchers have developed this novel single-cell level phenotypic assay that allows these two effects to be distinguished and compared quantitatively. Patient-derived viral sequences were cloned into an HIV-1 reporter virus. Flow cytometric analysis of single round infections allowed quantitative analysis of viral replication over a 4 log dynamic range. The assay faithfully reproduced known in vivo drug interactions occurring at the level of target cells. Simultaneous analysis of single round infections by wild type and resistant viruses in the presence and absence of the relevant drug combination divided the benefit of continued non-suppressive treatment into two additive components, residual virus susceptibility to the drug combination and selection for the drug-resistant variants with diminished replication capacity. Description (Set) Proposed Use (Set) This assay could be potentially used in the measurement of HIV drug resistance, an extremely important clinical problem.

Inventor(s): This invention provides an assay to simultaneously analyze residual susceptibility and reduced replication capacity of drug-resi

Type of Offer: Licensing



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