Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients

Curran, Adrían; Gutirerrez, Mar; Deig, Elisabet; Mateo, Gràcia; López, Rosa María; Imaz, Arkaitz; Crespo, Manuel; Ocaña, I; Domingo, Peré; Ribera, Esteban

doi:10.1093/jac/dkq295

Cited by 26 publications

(25 citation statements)

References 17 publications

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“…As it was reported by Corrêa and coworkers in a review paper, there are some studies applying high performance liquid chromatography (HPLC) with ultraviolet detector or mass spectrometer for determination of darunavir in biological samples and tablets [4][5][6][7][8][9]. Patel and coworkers developed a HPLC method for the estimation of darunavir in tablet dosage form using a C18 column and the effluents were monitored at 267 nm [9].…”

Section: Fig 1 Chemical Structure Of Darunavirmentioning

confidence: 99%

Development and Validation of First Derivative Spectrophotometric Method for Quantification of Darunavir in Tablets

Corrêa¹,

Serra²,

Salgado³

2014

BJPR

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Aims: Darunavir is widely used in HIV/AIDS therapy. It is a HIV protease inhibitor that has excellent efficacy against the virus. The aim of this study is to develop and validate an analytical method fast and free of interferences for determination of darunavir ethanolate as raw material and tablet dosage form. Methodology: As the formulation excipients show high interference in darunavir determination by a direct UV absorption measurement a derivative spectrophotometry was applied. A selective, easy and fast method was achieved employing simple and cheap instrumentation by using first-order derivative spectrophotometry. Results: The first-derivation of spectrum of the drug measured between 200 and 400 nm allowed identification of the analyte and showed absence of placebo interference. The assay was based on the absorbance at 276nm. The linear concentration range was established from 11 to 21 μg/mL. The intra-day and inter-day precision expressed as RSD was 0.06% and 3.75% respectively with mean recovery of 99.84%. Conclusion: The proposed analytical method is able to quantify darunavir as raw material and tablets and can be used routinely by any laboratory applying a spectrophotometer

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Section: Fig 1 Chemical Structure Of Darunavirmentioning

confidence: 99%

Development and Validation of First Derivative Spectrophotometric Method for Quantification of Darunavir in Tablets

Corrêa¹,

Serra²,

Salgado³

2014

BJPR

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“…Three virological failures were observed (> 400 copies / mL) in patients with DRV/r alone, undetected for DRV resistance mutations and subsequent viral resupresion after the reintroduction of NA. They review that two patients in the monotherapy group had clinical failure related to suppression of HIV in the central nervous system 11 . Also presented data from several studies that explore the possibility of another type of induction-maintenance is to initiate treatment with ATV / r and then suspend the RTV.…”

Section: Reducing the Number Of Drugsmentioning

confidence: 99%

Simplification of Antiretroviral Therapy (ART)

Martinez¹

2011

Recent Translational Research in HIV/AIDS

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Recent Translational Research in HIV/AIDS 238 reintroducing the previously recalled. The data at 96 weeks confirmed the durability and safety of this estrategia 3 . After this study, is performed OK04 study including 205 patients with undetectable VL for at least 6 months (median 28), who were taking HAART including LPV/r associated with two NA. Is a randomized, open, non-inferiority comparing the strategy of continuation of triple therapy compared to monotherapy with LPV/r, followed by reinduction with 2 NA if viral rebound appeared. At 48 weeks the percentage of patients without virologic failure was 90 and 94% respectively (difference, -4%, upper limit 95% CI for difference 3.4%, meeting the criteria for noninferiority). The percentage of patients with VL <;50 copies/mL at 48 weeks (ITT), considering as failures reinduction was 85% in the monotherapy group and 90% in the continuation (p = 0.31). Episodes of low-level viremia between 50 and 500 copies / mL were more frequent in patients treated with monotherapy (4 vs. none) 4 . With patients in these two studies performed a multivariate analysis of predictors of loss of virologic response in the group treated with LPV/r monotherapy. Virologic failure was associated with lack of grip, low haemoglobin levels and nadir CD4 <100 cells/μL 5 . In another study of simplification to monotherapy with LPV/r was somewhat different strategy. We included 155 previously untreated patients who were randomized 2:1 to treatment with ZDV/3TC start with LPV / r (n = 104) or EFV (n = 51). Within 24 weeks of treatment and after at least 3 controls with VL < 50 copies / mL, patients taking LPV maintenance came to LPV/r monotherapy. Whereas failure to any positive viremia at 96 weeks of follow up, 48% of patients treated with LPV / r and 61% with EFV had CVP < 50 copies / mL (p = 0.17, 95% of the difference, -29% to 4%). In a new analysis that included patients as responders to reintroduce them after getting back NA CVP < 50 copies / mL, 60% of patients on LPV/r and EFV 63% responded to treatment ( p = 0.73, CI 95% -19% 13%). Have been observed low viral loads in patients on monotherapy. As for security, lipoatrophy was observed in 5% of the monotherapy arm, compared to 34% of the EFV group. There were no differences in lipohypertrophy. Grade 3-4 lipid abnormalities were more frequent in the group of LPV/r. In these two studies highlights the importance of the period during which the CVP remains undetectable prior to the step alone. This same strategy is being explored and DRV/r 6,7 ATV/r 8,10 . They have published the results at 48 weeks of a pilot study, single-arm open-simplification to ATV / r, the ACTG 5201. Were included in the same 34 patients who started treatment with 2 NA and IP, who were with undetectable viral load (<50 copies / mL) for at least 48 weeks, had not been treated with NN or prior virologic failure were HBsAg negative. Upon entering the study were switched to IP they were taking on ATV / r and 6 weeks after suspending the AN. The primary endpoint was time to ...

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“…[6] DRV is a potent nonpeptidic HIV-1 PI. DRV has been shown to be an efficacious, safe, and well tolerated component of ARV regimens for triple-class (PI, non-nucleoside reverse transcriptase inhibitors [NNRTI], nucleoside reverse transcriptase inhibitors [NRTI]), treatment-experienced patients who switched regimens in the prospective Darunavir Outcomes Study, [7,8] and in treatment-experienced patients undergoing early salvage therapy. [8] Since multiple mutations in the HIV protease are generally necessary for the virus to demonstrate significant resistance to DRV or TPV, these drugs exhibit a high genetic barrier to the emergence of novel resistant strains.…”

Section: Introductionmentioning

confidence: 99%

“…DRV has been shown to be an efficacious, safe, and well tolerated component of ARV regimens for triple-class (PI, non-nucleoside reverse transcriptase inhibitors [NNRTI], nucleoside reverse transcriptase inhibitors [NRTI]), treatment-experienced patients who switched regimens in the prospective Darunavir Outcomes Study, [7,8] and in treatment-experienced patients undergoing early salvage therapy. [8] Since multiple mutations in the HIV protease are generally necessary for the virus to demonstrate significant resistance to DRV or TPV, these drugs exhibit a high genetic barrier to the emergence of novel resistant strains. [9,10] The POTENT (PrOspecTive EvaluatioN of Tipranavir vs. Darunavir in Treatment Experienced Patients) trial compared the safety and efficacy of TPV/r versus DRV plus low-dose ritonavir (DRV/r) when each was combined with an optimized background regimen (OBR) in triple-class-experienced, HIV-infected patients with resistance to more than one PI.…”

Section: Introductionmentioning

confidence: 99%

Boosted Tipranavir versus Darunavir in Treatment-Experienced Patients

Elgadi

Piliero

2011

Drugs R D

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Background: The POTENT trial compared the safety and efficacy of tipranavir/ ritonavir (TPV/r) to darunavir/ritonavir (DRV/r), each with an optimized background regimen (OBR) in triple-class experienced HIV-1-infected patients with resistance to more than one protease inhibitor (PI). Methodology/Principal Findings: POTENT was a prospective, open-label study of triple-class (PI, non-nucleoside reverse transcriptase inhibitors [NNRTI], nucleoside reverse transcriptase inhibitors [NRTI]), treatment-experienced, HIVpositive patients. Subjects were randomized to either TPV/r (500/200 mg twice daily) or DRV/r (600/100 mg twice daily) on a genotype-guided, investigatorselected OBR. CD4+ counts and HIV viral loads were assayed at key timepoints. The primary endpoint was time to virologic failure (viral load ‡500 copies/mL).POTENT was prematurely terminated due to slow enrollment. Thirty-nine patients were treated with either TPV/r (n = 19) or DRV/r (n = 20); 82% were male, 77% White, with mean age of 43.6 years. Mean baseline HIV RNA was 3.9 log 10 copies/mL. Median prior antiretrovirals was 11, with no prior raltegravir or maraviroc exposure. Raltegravir was the most common novel class agent in the OBRs (n = 14 TPV/r; n = 12 DRV/r). In both groups, patients achieved mean viral load decreases ‡2 log 10 copies/mL by week 8, and by week 12 mean CD4+ counts rose by 40-50 cells/mm

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Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients

Abstract: Darunavir/ritonavir at 900/100 mg once daily is highly effective, safe and well tolerated in treatment-experienced patients with no darunavir resistance, both in early salvage and switch strategies. Adequate drug plasma levels were achieved in all patients.

Cited by 26 publications

References 17 publications

Development and Validation of First Derivative Spectrophotometric Method for Quantification of Darunavir in Tablets

Development and Validation of First Derivative Spectrophotometric Method for Quantification of Darunavir in Tablets

Simplification of Antiretroviral Therapy (ART)

Boosted Tipranavir versus Darunavir in Treatment-Experienced Patients

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