Boffito M, Acosta E, Burger D, et al. Therapeutic drug monitoring and drug-drug interactions involving antiretroviral drugs
ABSTRACT The consensus of current international guidelines for the treatment of HIV infection is that data on therapeutic drug monitoring (TDM) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (Pls) provide a framework for the implementation of TDM in certain defined scenarios in clinical practice. However, the utility of TDM is considered to be on an individual basis until more data are obtained from large clinical trials showing the benefit of TDM. In April 2004, a panel of experts met for the second time in Rome, Italy. This was following the inaugural meeting in Perugia, Italy, in October 2000, which resulted in the manuscript published in AIDS 2002, 16(Suppl 1):S5-S37. The objectives of this second meeting were to review and update the numerous questions surrounding TDM of antiretroviral drugs and discuss the clinical utility, current concerns and future prospects of drug concentration monitoring in the care of HIV-1-infected individuals. A major focus of the meeting was to discuss and critically analyse recent and precedent clinical drug-drug interaction data to provide a clear framework of the pharmacological basis of how one drug may impact the disposition of another. This report, which has been updated to include material published or presented at international conferences up to the end of December 2004, reviews recent pivotal pharmacokinetic interaction data and provides advice to clinical care providers on how some drug-drug interactions may be prevented, avoided or managed, and, when data are available, on what dose adjustments and interventions should be performed.
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ABSTRACT: Because there are more than one million Americans with HIV, intensive care units continue to see frequent patients with HIV infection. In the era of highly active antiretroviral therapy, clinicians must be aware of drug toxicities and drug interactions. They must also recognize traditional opportunistic infections, as well as newer syndromes such as immune reconstitution syndrome, multicentric Castleman's disease, and primary pleural cell lymphoma.Proceedings of the American Thoracic Society 02/2006; 3(1):96-102. DOI:10.1513/pats.200511-122JH
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ABSTRACT: There is an increasing uptake of TDM of antiretroviral drugs, particularly in Europe. There is consensus that current antiretroviral drugs meet most of the criteria of drugs that can be considered as candidates for a TDM strategy. This review examines the pharmacokinetic-pharmacodynamic relationship for protease inibitors and non nucleoside reverse transcriptase inhibitor, give an overview of the published randomised clinical trials and then summarises the scenarios for use of TDM. Finally the development of the inhibitory quotient (IQ) concept is discussed.Therapeutic Drug Monitoring 07/2006; 28(3):468-73. DOI:10.1097/01.ftd.0000211825.57984.41 · 1.93 Impact Factor
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ABSTRACT: Mycobacterium tuberculosis is a concern in patients with human immunodeficiency virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical efficacy comparable to a standard of care regimen in naive patients and, when dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We evaluated here the safety and pharmacokinetics of ATV, resulting from three regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53) and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively. Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF) were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17), ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600-alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600, ATV area under the concentration-time curve values were comparable, but the C(min) values were lower relative to ATV 400 alone. ATV exposures were substantially reduced for the other RIF-containing regimens relative to ATV 400 alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF 400/200/600 treatments. Coadministration of ATV with RIF was safe and generally well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF should not be coadministered at the dosing regimens studied.Antimicrobial Agents and Chemotherapy 11/2006; 50(10):3336-42. DOI:10.1128/AAC.00461-06 · 4.45 Impact Factor