Mao-Song Tsai1, Sui-Yuan Chang2, Shu-Wen Lin3, Ching-Hua Kuo4, Hsin-Yun Sun5, Bin-Ru Wu6, Sue-Yo Tang5, Wen-Chun Liu5, Yi-Ching Su5, Chien-Ching Hung7, Shan-Chwen Chang5. 1. Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. 2. Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan. 3. Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan. 4. Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan. 5. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. 6. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan. 7. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan. Electronic address: hcc0401@ntu.edu.tw.
Abstract
BACKGROUND/ PURPOSE: Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infected patients is rarely investigated. METHODS: Consecutive patients with plasma human immunodeficiency virus RNA load < 200 copies/mL switching to unboosted atazanavir plus zidovudine-lamivudine (coformulated), abacavir-lamivudine (coformulated), or TDF/lamivudine > 3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load ≥ 200 copies/mL within 96 weeks. RESULTS: During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (p < 0.01). After a median follow-up duration of 96.0 weeks, treatment failure occurred in 19 (14.9%) and 34 (18.3%) patients in the TDF group and non-TDF group, respectively (p = 0.60). Low-level viremia (40-200 copies/mL) before switch (adjusted hazard ratio, 2.12; 95% confidence interval, 1.12-4.01) and without therapeutic drug monitoring (adjusted hazard ratio, 2.08; 95% confidence interval, 1.16-3.73) were risk factors for treatment failure. CONCLUSION: Switch to unboosted atazanavir with TDF/lamivudine achieves a similar treatment response to that with two other nucleoside reverse-transcriptase inhibitors in patients achieving virological suppression with the guidance of therapeutic drug monitoring.
BACKGROUND/ PURPOSE: Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infectedpatients is rarely investigated. METHODS: Consecutive patients with plasma human immunodeficiency virus RNA load < 200 copies/mL switching to unboosted atazanavir plus zidovudine-lamivudine (coformulated), abacavir-lamivudine (coformulated), or TDF/lamivudine > 3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load ≥ 200 copies/mL within 96 weeks. RESULTS: During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (p < 0.01). After a median follow-up duration of 96.0 weeks, treatment failure occurred in 19 (14.9%) and 34 (18.3%) patients in the TDF group and non-TDF group, respectively (p = 0.60). Low-level viremia (40-200 copies/mL) before switch (adjusted hazard ratio, 2.12; 95% confidence interval, 1.12-4.01) and without therapeutic drug monitoring (adjusted hazard ratio, 2.08; 95% confidence interval, 1.16-3.73) were risk factors for treatment failure. CONCLUSION: Switch to unboosted atazanavir with TDF/lamivudine achieves a similar treatment response to that with two other nucleoside reverse-transcriptase inhibitors in patients achieving virological suppression with the guidance of therapeutic drug monitoring.
Authors: JoEllyn M McMillan; Denise A Cobb; Zhiyi Lin; Mary G Banoub; Raghubendra S Dagur; Amanda A Branch Woods; Weimin Wang; Edward Makarov; Ted Kocher; Poonam S Joshi; Rolen M Quadros; Donald W Harms; Samuel M Cohen; Howard E Gendelman; Channabasavaiah B Gurumurthy; Santhi Gorantla; Larisa Y Poluektova Journal: J Pharmacol Exp Ther Date: 2018-02-23 Impact factor: 4.030