Abstract
Darunavir is an oral peptidomimetic HIV-1 protease inhibitor with antiretroviral activity against wild type HIV strains and HIV strains with protease inhibitor mutations. Ritonavir-boosted darunavir is rapidly absorbed and it has a higher bioavailability than unboosted darunavir. In HIV infected adults, the pharmacokinetic profile of darunavir showed that the drug concentrations are similar in the age range between 18 to 65 years and unaffected by the presence of moderate renal or hepatic function impairment. Darunavir chemical structure provides a strong interaction between the drug and HIV-1 protease and accounts for its potent antiretroviral activity and high genetic barrier to the development of resistance. The efficacy, safety and tolerability of darunavir have been widely demonstrated in HIV-infected treatment-experienced and naïve adult patients and it's use has been labelled in this population. Recently, upon the approval of the Food and Drug Administration, a 75 mg darunavir's tablet formulation has been licensed for the treatment of HIV-infected children and adolescents in the age range between 6 to 17 years.
Highlights
Effective antiretroviral combination therapy dramatically reduced HIV-related morbidity and mortality,[1,2] but the development of viral drug resistance, which occurs as a result of mutations in the viral genome,[3,4] continues to be responsible of treatment failure.Darunavir is a protease inhibitor (PI) recently approved in several countries of the European Union and in the United States
Ritonavir-boosted darunavir (DRV/r) demonstrated an in vitro substantial antiretroviral activity against wild-type HIV strains and HIV strains with protease inhibitors (PIs) mutations, and sustained efficacy and safety in naïve and treatmentexperienced HIV-infected patients.[5,6,7,8]
Pharmacokinetic parameters of darunavir administered orally with low-dose ritonavir tablet or solution formulations have been recently assessed in different studies on healthy volunteers and treatment-experienced and naïve HIV-infected patients.[9,10,11,12,13,14]
Summary
Effective antiretroviral combination therapy dramatically reduced HIV-related morbidity and mortality,[1,2] but the development of viral drug resistance, which occurs as a result of mutations in the viral genome,[3,4] continues to be responsible of treatment failure. POWER (Performance of TMC114/r When Evaluated in treatment-Experienced patients with PI resistance) 1 and POWER 2 were randomized, multicentre, 144 weeks phase IIb studies that compared the efficacy and safety of darunavir plus low-dose ritonavir versus investigator-select control PIs. The first 24 week of POWER 1 and 2 were partially blinded dose-finding studies,[63,64] followed by openlabel phases at 48,6 96,65 144 weeks.[66] POWER 3 is an analysis of two Phase IIb, noncomparative, open-label, 144-week trials in patients treated with darunavir/r 600/100 mg bid.[7,67] Inclusion criteria were: HIV infected-patients aged at least 18 years old with viral load 1000 copies/ml previously treated with highly active antiretroviral therapy (HAART defined as combination of 3 or more anti-viral drugs) for at least 3 months and having one or more PI mutations.
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