A novel bioanalytical method was developed and validated for the quantitative determination of darunavir（DRV） in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry（HILIC-MS...A novel bioanalytical method was developed and validated for the quantitative determination of darunavir（DRV） in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry（HILIC-MS/MS） with supported liquid extraction（SLE）.lrbesartan（IRB） was used as an internal standard（IS）.The analyte in rat plasma（200 μL） was isolated through SLE using ethyl acetate as the eluting solvent.The chromatographic separation was achieved on Luna-HILIC（250 mm × 4.6 mm,5 μm）column with a mobile phase of 0.1% of formic acid in water：acetonitrile（5：95,v/v）,at a constant flow rate of 1.0mL/min.The MS/MS ion transitions for DRV（548.1→392.0） and IS（429.2→207.1） were monitored on an ion trap mass spectrometer,operating in the multiple reaction monitoring（MRM） mode.The lower limit of quantitation（LLOQ） was 0.2 ng/mL and quantitation range was 0.2-5000 ng/mL.The method was validated for its selectivity,sensitivity,carryover,linearity,precision,accuracy,recovery,matrix effect and stability.The method was successfully applied to pharmacokinetic study in rats.展开更多
<strong>Background:</strong> A highly contagious virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a pandemic globally. HIV medications were one of the suggested treatmen...<strong>Background:</strong> A highly contagious virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a pandemic globally. HIV medications were one of the suggested treatments for Coronavirus disease 2019 (COVID-19). Here, we report an unusual adverse drug reaction with darunavir in a SARS-CoV-2-infected patient. <strong>Case Presentation:</strong> This is a case presentation of a 53-year-old male with no past medical history who was diagnosed with COVID-19. One week after initiating treatment, the patient developed acute kidney injury, and his serum creatinine increased significantly. <strong>Conclusion:</strong> As there was no clear justification for renal impairment such as a prerenal or postrenal cause, acute kidney injury, possibly crystal-induced nephropathy, was considered an adverse drug reaction from darunavir.展开更多
Background: Darunavir (DRV) is a useful antiretroviral treatment in the salvage therapy of multiclass-resistant HIV-infected patients. This study’s aim was to determine the frequency and risk factors for DRV resistan...Background: Darunavir (DRV) is a useful antiretroviral treatment in the salvage therapy of multiclass-resistant HIV-infected patients. This study’s aim was to determine the frequency and risk factors for DRV resistance-associated mutations (DRV-RAM) among DRV-naive Mexican patients with virologic failure after extensive antiretroviral treatment and exposure to at least one protease inhibitor (PI). Methods: HIV-infected patients with a history of at least 2 failed regimes were included and their clinical histories and genotype resistance tests were analyzed. Major PI resistance-associated mutations (PI-RAM), DRV-RAM and resistance to DRV were defined according to the IAS-USA criteria. Previous exposure to PI was compared between patients with DRV-resistant HIV and DRV-susceptible HIV-infected controls. Results: The median number of major PI-RAM was 2 (IQR = 0?- 3). In 54.7% (95% CI = 50.0% - 59.4%) of 631 subjects, no DRV-RAM were found on viral genotyping and 6.7% (95% CI = 4.8% - 8.6%) had 3 or more DRV-RAM. The two most frequently found DRV-RAM were in codons I84V (in 22.7% of cases) and L33F (in 20% of cases) in the viral protease gene. The number of major PI-RAM (as a surrogate marker of duration and number of PI used) and previous exposure to (fos) amprenavir or tipranavir were independently associated with DRV-resistant HIV infection. Conclusions: In this Mexican population, despite a high prior PI exposure, HIV-DRV resistance rate is relatively low and successful viral control with DRV-containing combined salvage therapy is expected in most patients.展开更多
Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patient...Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.展开更多
Background:COVID-19 remains a common threat to public health.In this study,we evaluated the antiviral effects and safety of Darunavir/Cobicisitat(DRV/c)in patients with confirmed COVID-19.Patients and Methods:We studi...Background:COVID-19 remains a common threat to public health.In this study,we evaluated the antiviral effects and safety of Darunavir/Cobicisitat(DRV/c)in patients with confirmed COVID-19.Patients and Methods:We studied 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11,2020.The patients were divided into the DRV/c and the control groups.The primary endpoint was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens.Results:Subjects with confirmed SARS-CoV-2 infection(n=66)were enrolled in this study;32 subjects were enrolled in the DRV/c group and 34 in the control group.The mean time to nucleic acid conversion(NAC)was shorter in the DRV/c group.The cumulative nucleic acid conversion rate(CNACR)in the DRV/c group was higher during the first two weeks,but the difference was not statistically significant.The proportion of fever during hospitalization in the DRV/c group was significantly lower than in the control group(P-value=0.01).It was found that,in the DRV/c group,the NAC of patients with a duration from symptom onset to admission within three days was significantly shorter(7.9±6.7 days)than in patients with a duration from symptom onset to admission above three days(15.9±7.1 days)(P=0.01).Conclusion:Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission,no significant differences were observed between the DRV/c group and the conventional therapy group,including the overall time to NAC,safety,and tolerability.展开更多
文摘A novel bioanalytical method was developed and validated for the quantitative determination of darunavir（DRV） in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry（HILIC-MS/MS） with supported liquid extraction（SLE）.lrbesartan（IRB） was used as an internal standard（IS）.The analyte in rat plasma（200 μL） was isolated through SLE using ethyl acetate as the eluting solvent.The chromatographic separation was achieved on Luna-HILIC（250 mm × 4.6 mm,5 μm）column with a mobile phase of 0.1% of formic acid in water：acetonitrile（5：95,v/v）,at a constant flow rate of 1.0mL/min.The MS/MS ion transitions for DRV（548.1→392.0） and IS（429.2→207.1） were monitored on an ion trap mass spectrometer,operating in the multiple reaction monitoring（MRM） mode.The lower limit of quantitation（LLOQ） was 0.2 ng/mL and quantitation range was 0.2-5000 ng/mL.The method was validated for its selectivity,sensitivity,carryover,linearity,precision,accuracy,recovery,matrix effect and stability.The method was successfully applied to pharmacokinetic study in rats.
文摘<strong>Background:</strong> A highly contagious virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a pandemic globally. HIV medications were one of the suggested treatments for Coronavirus disease 2019 (COVID-19). Here, we report an unusual adverse drug reaction with darunavir in a SARS-CoV-2-infected patient. <strong>Case Presentation:</strong> This is a case presentation of a 53-year-old male with no past medical history who was diagnosed with COVID-19. One week after initiating treatment, the patient developed acute kidney injury, and his serum creatinine increased significantly. <strong>Conclusion:</strong> As there was no clear justification for renal impairment such as a prerenal or postrenal cause, acute kidney injury, possibly crystal-induced nephropathy, was considered an adverse drug reaction from darunavir.
文摘Background: Darunavir (DRV) is a useful antiretroviral treatment in the salvage therapy of multiclass-resistant HIV-infected patients. This study’s aim was to determine the frequency and risk factors for DRV resistance-associated mutations (DRV-RAM) among DRV-naive Mexican patients with virologic failure after extensive antiretroviral treatment and exposure to at least one protease inhibitor (PI). Methods: HIV-infected patients with a history of at least 2 failed regimes were included and their clinical histories and genotype resistance tests were analyzed. Major PI resistance-associated mutations (PI-RAM), DRV-RAM and resistance to DRV were defined according to the IAS-USA criteria. Previous exposure to PI was compared between patients with DRV-resistant HIV and DRV-susceptible HIV-infected controls. Results: The median number of major PI-RAM was 2 (IQR = 0?- 3). In 54.7% (95% CI = 50.0% - 59.4%) of 631 subjects, no DRV-RAM were found on viral genotyping and 6.7% (95% CI = 4.8% - 8.6%) had 3 or more DRV-RAM. The two most frequently found DRV-RAM were in codons I84V (in 22.7% of cases) and L33F (in 20% of cases) in the viral protease gene. The number of major PI-RAM (as a surrogate marker of duration and number of PI used) and previous exposure to (fos) amprenavir or tipranavir were independently associated with DRV-resistant HIV infection. Conclusions: In this Mexican population, despite a high prior PI exposure, HIV-DRV resistance rate is relatively low and successful viral control with DRV-containing combined salvage therapy is expected in most patients.
文摘Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.
基金supported by the Key Project for Anti-2019 Novel Coronavirus Pneumonia from the National Key Research and Development Program of China(Grant No.2020YFC0845500)the Fundamental Research Funds for the Central Universities(Grant No.2042020kf1018).
文摘Background:COVID-19 remains a common threat to public health.In this study,we evaluated the antiviral effects and safety of Darunavir/Cobicisitat(DRV/c)in patients with confirmed COVID-19.Patients and Methods:We studied 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11,2020.The patients were divided into the DRV/c and the control groups.The primary endpoint was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens.Results:Subjects with confirmed SARS-CoV-2 infection(n=66)were enrolled in this study;32 subjects were enrolled in the DRV/c group and 34 in the control group.The mean time to nucleic acid conversion(NAC)was shorter in the DRV/c group.The cumulative nucleic acid conversion rate(CNACR)in the DRV/c group was higher during the first two weeks,but the difference was not statistically significant.The proportion of fever during hospitalization in the DRV/c group was significantly lower than in the control group(P-value=0.01).It was found that,in the DRV/c group,the NAC of patients with a duration from symptom onset to admission within three days was significantly shorter(7.9±6.7 days)than in patients with a duration from symptom onset to admission above three days(15.9±7.1 days)(P=0.01).Conclusion:Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission,no significant differences were observed between the DRV/c group and the conventional therapy group,including the overall time to NAC,safety,and tolerability.
