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J Acquir Immune Defic Syndr. 2010 Aug;54(4):389-93. doi: 10.1097/QAI.0b013e3181c42ea4.

Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy.

Author information

1
University of California, San Francisco, CA, USA. hhatano@php.ucsf.edu

Abstract

BACKGROUND:

Although integrase inhibitors are highly effective in the management of drug-resistant HIV, some patients fail to achieve durable viral suppression. The long-term consequences of integrase inhibitor failure have not been well defined.

METHODS:

We identified 29 individuals who exhibited evidence of incomplete viral suppression on a regimen containing an integrase inhibitor (23 raltegravir, 6 elvitegravir). Before initiating the integrase inhibitor-based regimen, the median CD4 T-cell count and plasma HIV RNA levels were 62 cells/mm and 4.65 log10 copies/mL, respectively.

RESULTS:

At the first failure time-point, the most common integrase resistance pattern for subjects taking raltegravir was wild-type, followed in order of frequency by Q148H/K/R+G140S, N155H, and Y143R/H/C. The most common resistance pattern for subjects taking elvitegravir was E92Q. Long-term failure was associated with continued viral evolution, emergence of high-level phenotypic resistance, and a decrease in replicative capacity.

CONCLUSIONS:

Although wild-type failure during early integrase inhibitor failure is common, most patients eventually develop high-level phenotypic drug resistance. This resistance evolution is gradual and associated with declines in replicative capacity.

PMID:
20300008
PMCID:
PMC2890029
DOI:
10.1097/QAI.0b013e3181c42ea4
[Indexed for MEDLINE]
Free PMC Article
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