Methods for determining resistance or susceptibility to HIV entry inhibitors
The invention provides a method for determining whether a human immunodeficiency virus is likely to be more resistant to a viral entry inhibitor than a reference HIV. In certain aspects, the methods comprise comparing the length of one or more variable regions of an envelope protein of the HIV or a number of glycosylation sites on the envelope protein of the HIV to a length of one or more corresponding variable regions of an envelope protein of the reference HIV or a number of glycosylation sites on the envelope protein of the reference HIV, wherein the HIV is likely to be more resistant to the CD4 binding site entry inhibitor than the reference HIV when the HIV has longer variable regions than the reference HIV or the HIV has more glycosylation sites than the reference HIV.
1. A method for treating a patient having a human immunodeficiency virus (HIV) infection, comprising
a) determining or having determined a length of one or more variable regions of an envelope protein of an HIV from a patient or determining or having determined a number of glycosylation sites on the envelope protein;
b) comparing or having compared the length of the one or more variable regions of the envelope protein of the HIV or the number of glycosylation sites on the envelope protein of the HIV to a length of one or more corresponding variable regions of an envelope protein of a reference HIV or a number of glycosylation sites on the envelope protein of the reference HIV, respectively,
c) determining or having determined that the HIV is likely to be less susceptible to a CD4 binding site entry inhibitor than the reference HIV if the one or more variable regions of the HIV are longer than corresponding variable regions of the reference HIV or if the HIV has more glycosylation sites than the reference HIV envelope protein; and
d) treating the patient with an effective amount of the CD4 binding site entry inhibitor if the HIV is determined in step c) to be likely to be susceptible to the CD4 binding site entry inhibitor, or treating the patient with an effective amount of a different inhibitor if the HIV is determined in step c) to be likely to have reduced susceptibility to the CD4 binding site entry inhibitor.
2. The method of claim 1 , wherein the CD4 binding site entry inhibitor is PRO542 or monoclonal antibody B12.
3. The method of claim 1 , wherein the reference HIV is NL4-3, HXB2, or SF2.
4. The method of claim 1 , wherein the HIV has at least one longer variable region than the reference HIV.
5. The method of claim 1 , wherein the HIV has at least one more glycosylation site than the reference HIV.
6. The method of claim 1 , wherein the HIV has at least one longer variable region and at least one more glycosylation site than the reference HIV.