Treatment response to unboosted atazanavir in combination with tenofovir disoproxil fumarate and lamivudine in human immunodeficiency virus-1-infected patients who have achieved virological suppression: A therapeutic drug monitoring and pharmacogenetic study
Journal
Journal of Microbiology, Immunology and Infection
Journal Volume
50
Journal Issue
6
Pages
789-797
Date Issued
2017
Author(s)
Tsai M.-S.
Wu B.-R.
Tang S.-Y.
Liu W.-C.
Su Y.-C.
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. ? 2016
SDGs
Other Subjects
abacavir plus lamivudine; atazanavir; cholesterol; glucuronosyltransferase 1A1; lamivudine; lamivudine plus tenofovir disoproxil; lamivudine plus zidovudine; multidrug resistance protein 1; pregnane X receptor; tenofovir disoproxil; triacylglycerol; virus RNA; ABC transporter subfamily B; ABCB1 protein, human; atazanavir; glucuronosyltransferase; Human immunodeficiency virus proteinase inhibitor; lamivudine; peroxisomal targeting signal 1 receptor; PEX5 protein, human; RNA directed DNA polymerase inhibitor; tenofovir; UGT1A1 enzyme; adult; aged; Article; comparative study; confidence interval; controlled study; drug blood level; drug monitoring; female; follow up; genotype; hazard ratio; human; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; hyperbilirubinemia; major clinical study; male; observational study; pharmacogenetic testing; retrospective study; risk factor; single nucleotide polymorphism; statistical significance; Taiwan; total cholesterol level; treatment failure; treatment outcome; treatment response; triacylglycerol blood level; virus inhibition; virus load; blood; chemically induced; drug combination; drug effect; genetics; Human immunodeficiency virus infection; hyperbilirubinemia; middle aged; pharmacogenetic testing; young adult; Adult; Aged; Atazanavir Sulfate; ATP Binding Cassette Transporter, Sub-Family B; Drug Combinations; Drug Monitoring; Female; Glucuronosyltransferase; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hyperbilirubinemia; Lamivudine; Male; Middle Aged; Peroxisome-Targeting Signal 1 Receptor; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Retrospective Studies; Reverse Transcriptase Inhibitors; Tenofovir; Treatment Failure; Viral Load; Young Adult
Type
journal article