Journal
THERAPEUTIC DRUG MONITORING
Volume 35, Issue 2, Pages 264-269Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FTD.0b013e3182834057
Keywords
atazanavir; tenofovir; drug interaction; therapeutic drug monitoring
Funding
- FRQS AIDS and Infectious Diseases Network
- Merck Canada
- Pfizer
- Schering-Plough
- Lundbeck
- Abbott Laboratories
- Bristol-Myers Squibb
- ViiV Healthcare
- Janssen
- Merck Frosst
- Gilead Sciences
- GlaxoSmithKline
- Boehringer Ingelheim
- Roche
- Tibotec
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Background: It is recommended to boost atazanavir with ritonavir (ATV/r) when it is combined with tenofovir disoproxil fumarate (TDF) because of drug interactions. For tolerability, unboosted atazanavir (ATV) is sometimes coadministered with TDF. The objective of this study was to evaluate the impact of this interaction on the proportion of patients achieving target ATV C-troughs and genotypic inhibitory quotients (GIQ). Materials and Methods: A therapeutic drug monitoring database was screened to evaluate ATV concentrations. Differences in C-trough and GIQ values among 4 antiretroviral drug combinations were evaluated. Results: Three hundred eight C-troughs, 91 GIQs, and 92 viral loads were evaluated for 238, 68, and 69 patients, respectively. Patients receiving ATV/r and TDF compared with ATV and TDF were more likely to have a therapeutic C-trough (odds ratio, 2.27; 95% confidence interval: 1.46-3.52; P < 0.001). Among patients on unboosted ATV, the odds of having a therapeutic ATV C-trough did not differ between groups with TDF versus without TDF. Although ritonavir increased the GIQ in patients receiving TDF (odds ratio, 3.38; 95% confidence interval: 1.30-8.81; P = 0.013), a similar proportion of patients on TDF and either ATV/r or ATV achieved a therapeutic GIQ. Conclusions: In patients receiving TDF, ritonavir increased the ATV C-trough and GIQ and patients on ATV/r were more likely to have therapeutic C-troughs. However, among subjects without ritonavir boosting, TDF compared with other nucleosides did not influence the odds of achieving a therapeutic ATV C-trough. These data suggest that ritonavir boosting of ATV is prudent, particularly in patients with resistance mutations.
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