Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase.

ABSTRACT:

Unlabelled

Dolutegravir (DTG) is the latest antiretroviral (ARV) approved for the treatment of human immunodeficiency virus (HIV) infection. The G118R substitution, previously identified with MK-2048 and raltegravir, may represent the initial substitution in a dolutegravir resistance pathway. We have found that subtype C integrase proteins have a low enzymatic cost associated with the G118R substitution, mostly at the strand transfer step of integration, compared to either subtype B or recombinant CRF02_AG proteins. Subtype B and circulating recombinant form AG (CRF02_AG) clonal viruses encoding G118R-bearing integrases were severely restricted in their viral replication capacity, and G118R/E138K-bearing viruses had various levels of resistance to dolutegravir, raltegravir, and elv

SUBMITTER: Quashie PK 

PROVIDER: S-EPMC4337543 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature