Combating HIV resistance - focus on darunavir.

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Tremblay CL

Combating HIV resistance - focus on darunavir.

Ther Clin Risk Manag. 2008 Aug;4(4):759-66.

PubMed ID

19209258 [ View in PubMed

]

Abstract

Darunavir is a second-generation protease inhibitor designed to have antiviral efficacy against HIV-1 isolates harboring multiple resistance mutations to protease inhibitors. Pivotal trials conducted in treatment-experienced HIV-infected individuals have demonstrated significantly greater virological suppression when darunavir was added to an optimized background treatment compared with a control protease inhibitor. This virological suppression was associated with an increase in CD4 counts and was sustained over time. Darunavir resistance-associated mutations have been defined as V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V, and L89V. In clinical trials, baseline darunavir susceptibility was a strong predictor of virological response. Prior use of fosamprenavir was associated with darunavir resistance mutations. Darunavir has a high genetic barrier and has a distinct resistance profile. Although some cross-resistance exists with other second-generation protease inhibitors such as tipranavir, different resistance mutation patterns have been observed upon failure to these regimens. It was found that mutations at 47V, 54M, 85V, and 73T were most prevalent in isolates resistant to both PIs. Mutations 48V, 50V, and 54L were associated with resistance to darunavir but not to tipranavir. 82S and 82T were associated with resistance to tipranavir but not to darunavir. Therefore, darunavir provides potent virological efficacy as well as high genetic barrier that can be useful to preserve treatment options in HIV-infected, treatment-experienced individuals.

DrugBank Data that Cites this Article

Drugs

Darunavir

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Darunavir	Human immunodeficiency virus type 1 protease	Protein	Human immunodeficiency virus 1	Yes	Inhibitor	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Darunavir	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details