Summary
When 400 mg of efavirenz once daily is given with anti-TB drugs, there is a slight decrease in EFV concentration. However, HIV viral loads remained suppressed and EFV concentrations were maintained within therapeutic limits. Hence, EFV 400 mg can be co-administered with anti-TB treatment. Still, this should be confirmed in TB+ PLWH. Moreover, while there is a slight decrease in concentration of EFV in the presence of high dose rifampin, EFV concentrations remain in the therapeutic window and HIV viral load is effectively suppressed when EFV is given at 600 mg and 800 mg in TB-HIV Infected Patients.
Sources
Efavirenz versus Rifampin
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Study Design
In this Nonblind, randomised, pharmacokinetic study, 24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis.Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600mg once daily (group A-1; n = 8) or efavirenz 800mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800mg once daily was added. Blood samples were obtained on days 7 and 14.Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions.
Study Results
There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800mg plus rifampicin were similar to those of efavirenz 600mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients’ bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >50kg were almost halved compared with those in patients weighing <50kg.
Study Conclusions
Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.
References
Lopez-Cortes LF, Ruiz-Valderas R, Viciana P, Alarcon-Gonzalez A, Gomez-Mateos J, Leon-Jimenez E, Pachon J. Pharmacokinetic interactions between efavirenz and rifampicin in hiv-infected patients with tuberculosis. Clinical Pharmacokinetics. 2002; 9: 681-690.
Efavirenz versus Rifampin
^
Study Design
All patients were started on TB treatment and initiated on ART 2-4 weeks after. They received isoniazid(H)/ pyrazinamide(Z)/ethambutol(E) and tenofovirDF/lamivudine at standard dosing during the first 8 weeks with Rifampin (R) 20mg/kg and efavirenz EFV 600mg (group G1); R 20mg/ kg and EFV 800mg (G2); R 10mg/kg and EFV 600mg (Control C). At 8 weeks of follow-up, all patients were switched to standard R and EFV doses. EFV plasma concentrations were assayed by validated High Performance Liquid Chromatography assay. The 90% confidence interval (CI) of the geometric mean ratios (GMR) of PK parameters with and without TB treatment was compared to the predefined 0.70-1.43 range for concentrations to remain within the therapeutic window. Plasma HIV-viral load (VL) was monitored 4, 12 and 24-26 weeks after ART initiation and mycobacterial sputum culture (Mycobacteria Growth Indicator Tube) 8 weeks after starting TB treatment.
Study Results
TB culture conversion was 85.7% (G1), 86.7% (G2) and 80.0% (C). At 12 weeks post-ART initiation, 92.6%, 86.2% and 92.6% of patients had VL < 400 copies/mL, respectively. No relationship could be evidenced between VL decline and EFV concentrations. The GMR (90% CI) of EFV+R/EFV plasma concentration (mg/ml) for C, G1, and G2 were respectively 0.92 (0.72- 1.08), 0.83 (0.72-1.00), and 1.16 (0.97-1.39). The GMR (90% CI) of EFV+R/EFV AUC (ug*hr/ml) for C, G1, and G2 were respectively 0.96 (0.84-1.09), 0.87 (0.75-1.00), and 1.12 (0.96-1.30).
Study Conclusions
Despite a trend to lower EFV concentrations when R dosing was doubled, concentration remained in the therapeutic window and there was no sign of decreased tolerance.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampin
^
Study Design
In this Nonblind, randomised, pharmacokinetic study, 24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis.Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600mg once daily (group A-1; n = 8) or efavirenz 800mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800mg once daily was added. Blood samples were obtained on days 7 and 14.Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions.
Study Results
There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800mg plus rifampicin were similar to those of efavirenz 600mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients’ bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >50kg were almost halved compared with those in patients weighing <50kg.
Study Conclusions
Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampin
^
Study Design
All patients were started on TB treatment and initiated on ART 2-4 weeks after. They received isoniazid(H)/ pyrazinamide(Z)/ethambutol(E) and tenofovirDF/lamivudine at standard dosing during the first 8 weeks with Rifampin (R) 20mg/kg and efavirenz EFV 600mg (group G1); R 20mg/ kg and EFV 800mg (G2); R 10mg/kg and EFV 600mg (Control C). At 8 weeks of follow-up, all patients were switched to standard R and EFV doses. EFV plasma concentrations were assayed by validated High Performance Liquid Chromatography assay. The 90% confidence interval (CI) of the geometric mean ratios (GMR) of PK parameters with and without TB treatment was compared to the predefined 0.70-1.43 range for concentrations to remain within the therapeutic window. Plasma HIV-viral load (VL) was monitored 4, 12 and 24-26 weeks after ART initiation and mycobacterial sputum culture (Mycobacteria Growth Indicator Tube) 8 weeks after starting TB treatment.
Study Results
TB culture conversion was 85.7% (G1), 86.7% (G2) and 80.0% (C). At 12 weeks post-ART initiation, 92.6%, 86.2% and 92.6% of patients had VL < 400 copies/mL, respectively. No relationship could be evidenced between VL decline and EFV concentrations. The GMR (90% CI) of EFV+R/EFV plasma concentration (mg/ml) for C, G1, and G2 were respectively 0.92 (0.72- 1.08), 0.83 (0.72-1.00), and 1.16 (0.97-1.39). The GMR (90% CI) of EFV+R/EFV AUC (ug*hr/ml) for C, G1, and G2 were respectively 0.96 (0.84-1.09), 0.87 (0.75-1.00), and 1.12 (0.96-1.30).
Study Conclusions
Despite a trend to lower EFV concentrations when R dosing was doubled, concentration remained in the therapeutic window and there was no sign of decreased tolerance.
References
Atwine, DH, Baudin, E, Gele, T. Efavirenz pharmacokinetics with rifampin double dose in tb-hiv infected patients. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampin
^
Study Design
All patients were started on TB treatment and initiated on ART 2-4 weeks after. They received isoniazid(H)/ pyrazinamide(Z)/ethambutol(E) and tenofovirDF/lamivudine at standard dosing during the first 8 weeks with Rifampin (R) 20mg/kg and efavirenz EFV 600mg (group G1); R 20mg/ kg and EFV 800mg (G2); R 10mg/kg and EFV 600mg (Control C). At 8 weeks of follow-up, all patients were switched to standard R and EFV doses. EFV plasma concentrations were assayed by validated High Performance Liquid Chromatography assay. The 90% confidence interval (CI) of the geometric mean ratios (GMR) of PK parameters with and without TB treatment was compared to the predefined 0.70-1.43 range for concentrations to remain within the therapeutic window. Plasma HIV-viral load (VL) was monitored 4, 12 and 24-26 weeks after ART initiation and mycobacterial sputum culture (Mycobacteria Growth Indicator Tube) 8 weeks after starting TB treatment.
Study Results
TB culture conversion was 85.7% (G1), 86.7% (G2) and 80.0% (C). At 12 weeks post-ART initiation, 92.6%, 86.2% and 92.6% of patients had VL < 400 copies/mL, respectively. No relationship could be evidenced between VL decline and EFV concentrations. The GMR (90% CI) of EFV+R/EFV plasma concentration (mg/ml) for C, G1, and G2 were respectively 0.92 (0.72- 1.08), 0.83 (0.72-1.00), and 1.16 (0.97-1.39). The GMR (90% CI) of EFV+R/EFV AUC (ug*hr/ml) for C, G1, and G2 were respectively 0.96 (0.84-1.09), 0.87 (0.75-1.00), and 1.12 (0.96-1.30).
Study Conclusions
Despite a trend to lower EFV concentrations when R dosing was doubled, concentration remained in the therapeutic window and there was no sign of decreased tolerance.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94). 11/22 subjects were carriers of 516T (10) and/or 938C (3) slow metabolizers alleles.
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
^
Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampicin
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Study Design
This open-label study investigated the pharmacokinetics (PK), efficacy, CYP2B6 pharmacogenetics of efavirenz (EFV)400 + Isoniazid/Rifampicin (INH/RIF) in patients living with HIV/AIDS (PLWH) without TB (TB-), receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600mg with a viral load (VL)< 50 copies/mL. They were switched to TDF/FTC/ EFV400. Weekly therapeutic drug monitoring (TDM), steady-state PK profiles of EFV400 without (PK1) and with INH/RIF following 4 (PK2) and 12 (PK3) weeks of co-administration, safety, virologic efficacy, polymorphisms in CYP2B6 (516C>T; 938T>C) were evaluated.
Study Results
All had VL<50 at baseline, which was maintained throughout the study. Geometric mean ratios (GMR) PK2/PK1, n=22 (90%CI) of EFV400 Cmax, AUC, and C24h were 0.91 (0.83-0.99), 0.91 (0.86-1.13), 0.85 (0.72-0.99). GMR (90%CI) of PK3/PK2 and PK3/PK1 (n=17) Cmax, AUC, and C24h were 0.97 (0.88- 1.06), 0.94 (0.88-1.06), 0.91 (0.78-1.05) and 0.85 (0.78-0.94), 0.86 (0.80-1.09), 0.77 (0.64-0.94).
Study Conclusions
INH/RIF co-administration in TB-PLWH with a VL<50 was associated with limited changes in EFV400 exposure (<23%). Results from this cohort conclude that EFV400 can be co-administered with anti-TB treatment. This should be confirmed in TB+ PLWH.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampin
^
Study Design
In this Nonblind, randomised, pharmacokinetic study, 24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis.Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600mg once daily (group A-1; n = 8) or efavirenz 800mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800mg once daily was added. Blood samples were obtained on days 7 and 14.Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions.
Study Results
There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800mg plus rifampicin were similar to those of efavirenz 600mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients’ bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >50kg were almost halved compared with those in patients weighing <50kg.
Study Conclusions
Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampin
^
Study Design
In this Nonblind, randomised, pharmacokinetic study, 24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis.Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600mg once daily (group A-1; n = 8) or efavirenz 800mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800mg once daily was added. Blood samples were obtained on days 7 and 14.Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions.
Study Results
There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800mg plus rifampicin were similar to those of efavirenz 600mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients’ bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >50kg were almost halved compared with those in patients weighing <50kg.
Study Conclusions
Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Rifampin
^
Study Design
All patients were started on TB treatment and initiated on ART 2-4 weeks after. They received isoniazid(H)/ pyrazinamide(Z)/ethambutol(E) and tenofovirDF/lamivudine at standard dosing during the first 8 weeks with Rifampin (R) 20mg/kg and efavirenz EFV 600mg (group G1); R 20mg/ kg and EFV 800mg (G2); R 10mg/kg and EFV 600mg (Control C). At 8 weeks of follow-up, all patients were switched to standard R and EFV doses. EFV plasma concentrations were assayed by validated High Performance Liquid Chromatography assay. The 90% confidence interval (CI) of the geometric mean ratios (GMR) of PK parameters with and without TB treatment was compared to the predefined 0.70-1.43 range for concentrations to remain within the therapeutic window. Plasma HIV-viral load (VL) was monitored 4, 12 and 24-26 weeks after ART initiation and mycobacterial sputum culture (Mycobacteria Growth Indicator Tube) 8 weeks after starting TB treatment.
Study Results
TB culture conversion was 85.7% (G1), 86.7% (G2) and 80.0% (C). At 12 weeks post-ART initiation, 92.6%, 86.2% and 92.6% of patients had VL < 400 copies/mL, respectively. No relationship could be evidenced between VL decline and EFV concentrations. The GMR (90% CI) of EFV+R/EFV plasma concentration (mg/ml) for C, G1, and G2 were respectively 0.92 (0.72- 1.08), 0.83 (0.72-1.00), and 1.16 (0.97-1.39). The GMR (90% CI) of EFV+R/EFV AUC (ug*hr/ml) for C, G1, and G2 were respectively 0.96 (0.84-1.09), 0.87 (0.75-1.00), and 1.12 (0.96-1.30).
Study Conclusions
Despite a trend to lower EFV concentrations when R dosing was doubled, concentration remained in the therapeutic window and there was no sign of decreased tolerance.
References
Cerrone, M, Wang, X, Neary, M. Pharmacokinetics of efavirenz 400mg with isoniazid/ rifampicin in people with hiv. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
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