Compositions and methods for determining resistance to inhibitors of virus entry using recombinant virus assays
AssigneeMonogram Biosciences, Inc.
InventorChristos J. Petropoulos
Life of this patent
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Abstract
The invention provides a method for determining whether a human immunodeficiency virus is resistant to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.
Claims15
A method for treating a patient having an infection with a population of human immunodeficiency virus (HIV) viral particles, comprising:
- (a) contacting or having contacted a plurality of HIV viral particles from a patient having an infection with a first population of HIV viral particles with a cell in the presence of an HIV entry inhibitor, wherein the plurality of HIV viral particles were obtained from the patient at a first time point, wherein the cell expresses a cell surface receptor to which the viral particles bind, and wherein the cell or the viral particle comprises an indicator nucleic acid that produces a detectable signal when the viral particle enters into the cell,
- (b) collecting or having collected data points that measure entry of the first HIV population into the cell by measuring the amount of the detectable signal produced by the cell in the presence of varying concentrations of the HIV entry inhibitor;
- (c) generating a log-sigmoid inhibition curve comprising the data points showing the maximum inhibition percentage for the first HIV population;
- (d) comparing the maximum inhibition percentage of the inhibition curve of step (c) to the maximum inhibition percentage of a log-sigmoid inhibition curve for a second HIV population, wherein the second HIV population comprises a plurality of HIV viral particles that were later obtained from the patient at a second time point;
- (e) determining that the second HIV population has reduced susceptibility to the HIV entry inhibitor if the maximum inhibition percentage observed for the second HIV population is lower than the maximum inhibition percentage observed for the first HIV population or if the entry of the second HIV population cannot be completely inhibited by the HIV entry inhibitor;
- and
- (f) treating the patient with an effective amount of the HIV entry inhibitor if the maximum inhibition percentage observed for the second HIV population is the same as or higher than the maximum inhibition percentage observed for the first HIV population or if the entry of the second HIV population can be completely inhibited by the HIV entry inhibitor, or treating the patient with an effective amount of a different HIV entry inhibitor or other HIV inhibitor if the maximum inhibition percentage observed for the second HIV population is lower than the maximum inhibition percentage observed for the first HIV population or if the entry of the second HIV population cannot be completely inhibited by the HIV entry inhibitor.
Dependencies are inferred from the claim text.