405Therapy Edge Spain to develop personalized antiviral treatment strategies for
patients with chronic hepatitis C or B. Other partners include the Vall d’Hebron
Institute of Research and the Networking Biomedical Research Centre in Liver and
Digestive Diseases, which is comprised of eight research groups. Roche will use its
454 sequencing systems and bioinformatics analysis, coupled with other genetic
and molecular analysis techniques, to apply massively parallel sequencing in
developing personalized antiviral treatments for chronic sufferers. HCV and HBV
exhibit great variability; a person infected with one of these viruses presents a
complex population of variants comprising a structure known as ‘quasi-species’.
The identifi cation of these variants may be crucial for avoiding the selection of
variants resistant to the new antiviral therapies. Using 454 sequencing makes it
possible to create a comprehensive profi le of the complex viral populations that
circulate in individuals in order to identify the quasi-species that are resistant to
existing antiviral treatments.
ViroSeq® HCV Assay (Celera), sequence-based test, is in development for
detection of resistance to HCV therapy. To effectively manage patient treatment
decisions as new therapeutics become available, HCV resistance testing will become
standard of care.
Personalized Management of Fungal Infections
Treatment or prophylaxis of invasive fungal infection in recipients of hematopoietic
stem cell transplant (HSCT) may require management of coexistent malnutrition,
organ dysfunction and graft versus host disease, all of which create added poten-
tial for inter – and intra-patient variations in drug metabolism as well as drug
interactions. Polymorphism is common in genes encoding pathway components
of antifungal drug metabolism such as enzymes (cytochrome P450 (CYP450),
glutathione S-transferase, N-acetyltransferase and uridine 5′-diphospho-
glucuronosyltransferase), uptake transporters (organic cationic transporter, novel
organic cationic transporter, organic anion transporter protein, organic anion trans-
port, and peptide tranporter) and effl ux transporters (breast cancer resistance pro-
tein, bile sale export pump, multidrug and toxin extrusion type transporter, multidrug
resistance protein, permeability glycoprotein, and urate transporter). Specifi c poly-
morphisms may be generalized throughout a population or largely confi ned to eth-
nic groups. CYP450 enzymes, especially 2C9 and 2C19, exhibit extensive
polymorphism and are central to the metabolism of azole antifungals and their inter-
actions with other drugs including calcineurin inhibitors, cytotoxics and benzodiaz-
epines. Polymorphism may ultimately affect drug effi cacy: CYP2C19 variation
leads to a fi vefold variation in voriconazole levels between individuals. In the future,
routine provision of pharmacogenomic data for new drugs together with accumulat-
ing knowledge about established agents will challenge physicians to assimilate and
apply that information in drug prescribing (Ashbee and Gilleece 2011 ).
Personalized Management of Fungal Infections