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Darunavir

Prezista is the trade name.

A protease inhibitor drug used to treat HIV infection.

A recommended treatment option for treatment-naïve and previously treated adults and adolescents.

A second-generation protease inhibitor (PIs), to overcome problems with the older agents in this class, such as indinavir.

An oral agent with bioavailability of 37% without ritonavir, and 82% with ritonavir.

Protein binding of 95% and hepatic metabolism, with half-life of15 hours.

80% excreted if feces and 14% in urine.

A treatment option for patients with drug-resistant HIV.

Targets HIV-1 protease, a protein that performs an essential function in the lifecycle of HIV.

HIV-1 protease breaks up the viral polypeptide into components that can be used to form mature virus particles.

The mature HIV virus is translated onto a long polypeptide strand.

Protease inhibitors act as noncovalent inhibitors of HIV protease, halting the HIV lifecycle as the protein components for new viral particles are unable to be produced.

A nonpeptidic inhibitor of protease receptor that lodges itself in the active site of protease receptor hydrogen bonds.

Increases interactions with HIV-1 protease and is more resistant against HIV-1 protease mutations.

Has a much stronger interaction with ” and its dissociation constant is 1/100 to 1/1000 of other protease inhibitors.

It’s strong interaction comes from increased hydrogen bonds between darunavir and the backbone of the protease receptor active site.

Creates more hydrogen bonds with the proteas receptor active site than most PIs and the PR-PI interaction is less likely to be disrupted by a mutation.

A recommended treatment for treatment-naïve and treatment-experienced adults and adolescents.

Has comparable efficacy to lopinavir/ritonavir at 96 weeks with a once-daily dosing in treatment-naïve patients, and has shown superiority to lopinavir/ritonavir and other protease inhibitors in the POWER trials.

ARTEMIS trial included 689 treatment-naive participants who were randomly assigned to receive 800/100 mg once-daily darunavir/ritonavir or 800/200 mg lopinavir/ritonavir given once- or twice-daily: At 96 weeks, darunavir/ritonavir remained non inferior to lopinavir/ritonavir, but significantly more patients in the darunavir/ritonavir arm achieved HIV RNA below 50 copies/ml compared with the lopinavir/ritonavir arm.

Once-daily darunavir/ritonavir is safe and well tolerated.

About 71% of patients in the darunavir/ritonavir arm reached an undetectable viral load (less than 50 copies/ml) vs. 60% of patients in the lopinavir/ritonavir arm, about 10% of patients in the darunavir/ritonavir arm experienced virological failure vs. 22% of patients in the lopinavir/ritonavir arm.

In the above study 21% of patients in the darunavir/ritonavir arm developed primary PI resistance mutations vs. 36% of patients in the lopinavir/ritonavir arm, and 14% of patients in the darunavir/ritonavir arm developed primary NRTI resistance mutations vs. 27% of patients in the lopinavir/ritonavir arm.

Significantly more patients achieved a reduction in viral load at the 24-week primary endpoint, almost four times as many patients (45%) have achieved an undetectable viral load with the darunavir-containing regimen..

In previously treated patients, the darunavir containing regimen increased CD4 cell counts five times more than other PI arm.

Does not cure HIV infection or AIDS, and does not prevent passing HIV to others.

Generally well tolerated, with mild to moderate rash in 7% of patients.

Moderate to severe side effects include diarrhea (2.3%), headache (3.8%), abdominal pain (2.3%), constipation (2.3%), and vomiting (1.5%).

Four percent of patients discontinued treatment due to adverse events.

Drug interactions with other medications commonly used in HIV patient populations are few, such as other antiretroviral medications, proton pump inhibitors, and H2 receptor antagonists.

St. John’s wort may reduce its effectiveness by interaction with CYP3A.

Should be used with caution in patients with hepatic impairment.

High blood sugar, diabetes or worsening of diabetes, muscle pain, tenderness or weakness, and increased bleeding in people with hemophilia have been reported.

Changes in body fat have been seen in some patients.

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