antiretrovirals; clinical pharmacokinetics; pharmacogenetics; metabolite profiling; liquid chromatography tandem mass spectrometry; Swiss HIV Cohort Study
Glass Tracy R, Rotger Margalida, Telenti Amalio, Decosterd Laurent, Csajka Chantal, Bucher Heiner C, Günthard Huldrych F, Rickenbach Martin, Nicca Dunja, Hirschel Bernard, Bernasconi Enos, Wandeler Gilles, Battegay Manuel, Marzolini Catia, Swiss HIV Cohort Study (2012), Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy., in
PloS one, 7(1), 29186-29186.
Arab-Alameddine Mona, Fayet-Mello Aurélie, Lubomirov Rubin, Neely Michael, di Iulio Julia, Owen Andrew, Boffito Marta, Cavassini Matthias, Günthard Huldrych F, Rentsch Katharina, Buclin Thierry, Aouri Manel, Telenti Amalio, Decosterd Laurent Arthur, Rotger Margalida, Csajka Chantal, Swiss HIV Cohort Study Group (2012), Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals., in
Antimicrobial agents and chemotherapy, 56(6), 2959-66.
Csajka C, Marchetti O, Manuel O, Decosterd LA, Telenti A (2012), Antimicrobial agents, in U. Zanger, P. Anzenbacher (ed.), Wiley/Verlag Chemie , Weinheim , 379-402.
Aouri M., Decosterd L. A., Buclin T., Hirschel B., Calmy A., Livio F. (2012), Drug interactions between voriconazole, darunavir/ritonavir and etravirine in an HIV-infected patient with Aspergillus pneumonia, in
AIDS, 26, 776-778.
Telenti A. (2012), HIV and Antiretroviral Therapy. Principles of Pharmacogenetics and Pharmacogenomics,, in Russ B. Altman, David B. Goldstein, David Flockhart (ed.), Cambridge University Press, UK, 238-248.
Guidi M, Arab-Alameddine M, Rotger M, Aouri M, Telenti A, Decosterd LA, Buclin T, Csajka C (2012), Dosage optimization of treatments using population pharmacokinetic modeling and simulation, in
Chimia, 66, 291-295.
Fayet Mello Aurélie, Buclin Thierry, Decosterd Laurent A, Delhumeau Cécile, di Iulio Julia, Fleurent Alessandra, Schneider Marie-Paule, Cavassini Matthias, Telenti Amalio, Hirschel Bernard, Calmy Alexandra (2011), Successful efavirenz dose reduction guided by therapeutic drug monitoring., in
Antiviral therapy, 16(2), 189-97.
Haas D. W., Kuritzkes D. R., Ritchie M. D., Amur S., Gage B. F., Maartens G., Masys D., Fellay J., Phillips E., Ribaudo H. J., Freedberg K. A., Petropoulos C., Manolio T. A., Gulick R. M., Haubrich R., Kim P., Dehlinger M., Abebe R., Telenti A. (2011), Pharmacogenomics of HIV therapy: summary of a workshop sponsored by the National Institute of Allergy and Infectious Diseases, in
HIV Clin Trials, 12, 277-285.
Fayet Mello Aurélie, Buclin Thierry, Franc Claudia, Colombo Sara, Cruchon Sandra, Guignard Nicole, Biollaz Jérôme, Telenti Amalio, Decosterd Laurent A, Cavassini Matthias (2011), Cell disposition of raltegravir and newer antiretrovirals in HIV-infected patients: high inter-individual variability in raltegravir cellular penetration., in
The Journal of antimicrobial chemotherapy, 66(7), 1573-81.
Arab-Alameddine Mona, Décosterd Laurent Arhtur, Buclin Thierry, Telenti Amalio, Csajka Chantal (2011), Antiretroviral drug toxicity in relation to pharmacokinetics, metabolic profile and pharmacogenetics., in
Expert opinion on drug metabolism & toxicology, 7, 609-622.
Ortiz M., Poloni E. S., Furrer H., Kovari H., Martinez R., Arnedo M., Elzi L., Bernasconi E., Vernazza P., Hirschel B., Cavassini M., Ledergerber B., Gunthard H. F., Telenti A., Tarr P. E. (2011), No longitudinal mitochondrial DNA sequence changes in HIV-infected individuals with and without lipoatrophy, in
The Journal of infectious diseases, 203, 620-624.
Lubomirov Rubin, Colombo Sara, di Iulio Julia, Ledergerber Bruno, Martinez Raquel, Cavassini Matthias, Hirschel Bernard, Bernasconi Enos, Elzi Luigia, Vernazza Pietro, Furrer Hansjakob, Günthard Huldrych F, Telenti Amalio, Swiss HIV Cohort Study (2011), Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study., in
The Journal of infectious diseases, 203(2), 246-57.
Nguyen Alain, Calmy Alexandra, Delhumeau Cécile, Mercier Isabelle K, Cavassini Matthias, Fayet-Mello Aurélie, Elzi Luigia, Genné Daniel, Rauch Andri, Bernasconi Enos, Hirschel Bernard, Swiss HIV Cohort Study (2011), A randomized crossover study to compare efavirenz and etravirine treatment., in
AIDS (London, England), 25(1), 57-63.
Neely Michael, Decosterd Laurent, Fayet Aurélie, Lee Janice Soo Fern, Margol Ashley, Kanani Meera, di Iulio Julia, von Schoen-Angerer Tido, Jelliffe Roger, Calmy Alexandra (2010), Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers., in
Antimicrobial agents and chemotherapy, 54(11), 4619-25.
Tarr P. E., Telenti A. (2010), Genetic screening for metabolic and age-related complications in HIV-infected persons, in
F1000 Med Rep, 2(83), 1-5.
Rotger M., Gsponer T., Martinez R., Taffe P., Elzi L., Vernazza P., Cavassini M., Bernasconi E., Hirschel B, Furrer H., Weber R., Ledergerber B., Egger M., Telenti A., Tarr P. E. (2010), Impact of single nucleotide polymorphisms and of clinical risk factors on new-onset diabetes mellitus in HIV-infected individuals, in
Clinical infectious diseases , 51(2010), 1090-1098.
Lubomirov Rubin, di Iulio Julia, Fayet Aurélie, Colombo Sara, Martinez Raquel, Marzolini Catia, Furrer Hansjakob, Vernazza Pietro, Calmy Alexandra, Cavassini Matthias, Ledergerber Bruno, Rentsch Katharina, Descombes Patrick, Buclin Thierry, Decosterd Laurent A, Csajka Chantal, Telenti Amalio, Swiss HIV Cohort Study (2010), ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir., in
Pharmacogenetics and genomics, 20(4), 217-30.
Tarr P. E., Rotger M., Telenti A. (2010), Dyslipidemia in HIV-infected individuals: from pharmacogenetics to pharmacogenomics, in
Pharmacogenomics, 11, 587-594.
Fayet A, Beguin A, de Tejada BM (2010), Determination of Unbound Antiretroviral Drug Concentrations by a Modified Ultrafiltration Method Reveals High Variability in the Free Fraction (vol 30, pg 511, 2008), in
THERAPEUTIC DRUG MONITORING, 32(1), 117-117.
Rotger M., Bayard C., Taffe P., Martinez R., Cavassini M., Bernasconi E., Battegay M., Hirschel B., Furrer H., Witteck A., Weber R., Ledergerber B., Telenti A., Tarr P. E. (2009), Contribution of genome-wide significant single-nucleotide polymorphisms and antiretroviral therapy to dyslipidemia in HIV-infected individuals: a longitudinal study, in
Circulation. Cardiovascular genetics, 2, 621-628.
Arab-Alameddine M, Di Iulio J, Buclin T, Rotger M, Lubomirov R, Cavassini M, Fayet A, Décosterd L A, Eap C B, Biollaz J, Telenti A, Csajka C, Swiss HIV Cohort Study (2009), Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals., in
Clinical pharmacology and therapeutics, 85(5), 485-94.
di Iulio Julia, Fayet Aurélie, Arab-Alameddine Mona, Rotger Margalida, Lubomirov Rubin, Cavassini Matthias, Furrer Hansjakob, Günthard Huldrych F, Colombo Sara, Csajka Chantal, Eap Chin B, Decosterd Laurent A, Telenti Amalio, Swiss HIV Cohort Study (2009), In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function., in
Pharmacogenetics and genomics, 19(4), 300-9.
Telenti A (2009), Time (again) for a randomized trial of pharmacogenetics of antiretroviral therapy, in
Pharmacogenomics, 10, 515-516.
Fayet A, Béguin A, Zanolari B, Cruchon S, Guignard N, Telenti A, Cavassini M, Günthard H F, Buclin T, Biollaz J, Rochat B, Decosterd L A (2009), A LC-tandem MS assay for the simultaneous measurement of new antiretroviral agents: Raltegravir, maraviroc, darunavir, and etravirine., in
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 877(11-12), 1057-69.
Fayet A, Beguin A, de Tejada BM, Colombo S, Cavassini M, Gerber S, Eap CB, Telenti A, Buclin T, Biollaz J, Decosterd LA (2008), Determination of unbound antiretroviral drug concentrations by a modified ultrafiltration method reveals high variability in the free fraction, in
THERAPEUTIC DRUG MONITORING, 30(4), 511-522.
Fayet-Mello A, Buclin T, Guignard N, Cruchon S, Cavassini M, Grawe C, Gremlich E, Aebi Popp K, Schmid F, Eap CB, Telenti A, Biollaz J, Decosterd LA*, Martinez de Tejada B*, Free and total plasma levels of lopinavir during pregnancy, at delivery and in post-partum: implication for dosage adjustments in pregnant women, in
Antiviral Therapy, in press.
Siccardi M, Almond L, Schipani A, Csajka C, Marzolini C, Wyen C, Brockmeyer N H, Boffito M, Owen A, Back D, Pharmacokinetic and Pharmacodynamic Analysis of Efavirenz Dose Reduction Using an In Vitro-In Vivo Extrapolation Model., in
Clinical pharmacology and therapeutics.
Clinical pharmacokinetic and pharmacogenetic research efforts have been pursued in HIV therapeutics because of the prevalence of toxicity, the life-long nature of treatment, and the complexity inherent to multidrug therapy. Drug pharmacokinetics is a phenotypic trait influenced by complex genetic and non-genetic factors affecting drug transport and metabolism. Pharmacogenetics aim at determining patients genetic predisposition influencing drug exposure, toxicity and clinical response. Current approaches in pharmacokinetics have focused almost exclusively the parent drug concentrations. Current approaches in pharmacogenetics have examined one or few candidate genes for a limited number of allelic variants. Over the last funding period we have:1.Developed methodologies by using a new capacity of technical tools (mass spectrometry facility, triple quadripole and linear trap instruments), massive and facilitated access to integrated pharmacology and genetics databases, population pharmacokinetics expertise (NONMEM) and pharmacogenetics plateforms for high throughput genotyping and genome analysis. 2.Completed a number of coordinated research projects integrating basic and applied pharmacogenetic, pharmacokinetic and pharmacodynamic aspects of HIV therapy.The current proposal addresses the:1.Pharmacology and pharmacogenetics of new antiretroviral drugs.2.Integration of drug metabolite profiling and whole ADME pharmacogenetics analysis. 3.Development of population pharmacokinetic/pharmacogenetics models.4.Translation to a number of clinical studies aiming at validating the usefulness of new pharmacokinetic and pharmacogenetic tools. The proposed strategy aims at increasing the current understanding of the complex gene-environmental interplay influencing toxicity and efficacy of antiretroviral treatment at the patient and the population levels, thus offering new possibilities for improving the long term tolerability and response to antiretroviral treatments.