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Volume 50, Number 6, December 2017

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 


Mao-Song Tsai, Sui-Yuan Chang, Shu-Wen Lin, Ching-Hua Kuo, Hsin-Yun Sun, Bin-Ru Wu, Sue-Yo Tang, Wen-Chun Liu, Yi-Ching Su, Chien-Ching Hung, Shan-Chwen Chang


 

Corresponding author:

Chien-Ching Hung, Corresponding author. Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. 



 

Background and 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. 



 

Key words:

antiretroviral agent, combination antiretroviral therapy, drug–drug interaction, nucleoside reverse-transcriptase inhibitor, protease inhibitor