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Anti-HIV Therapy: every patient is unique Pharmacogenetics of antiretroviral therapy
“Every patient is unique”… This sentence, applied to pharmacogenetics, is as neat and true as in no other field of Medicine.
Pharmacogenetics is defined as the studying of correlations between genetic characteristics and response to therapy and it can found various fields of application in antiretroviral treatment.
Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors usage has obtained enormous results in HIV-positive patients but failure and thus selection of resistance mutations is still a possibility. Various studies showed how plasmatic concentrations of different drugs are related to therapeutic efficacy: these data indicated TDM as one the essential instruments to optimize treatment. The wide interindividual variability in drug concentration, related to the possibility of failure, can be caused by factors such as diet and concomitant drugs but also by genetic factors responsible of modifying enzymes implicated in drug disposition and metabolism. Besides pharmacokinetic variability the role of genetic polymorphisms has been studied in HIV evolution and pathogenicity, as, for example, in viral replication and immune system depletion. Furthermore some drugs toxicity can be predicted by genetic polymorphisms that create predisposition to that adverse effect.
Our Laboratory developed and studied some tests for identifying polymorphisms in genes involved in drug disposition and metabolism:
- C3435T for P-Glycoprotein (membrane transporter for various antiretroviral drugs)
- CYP3A5*3 and
*6 of cytocrome P450 (involved in PIs metabolism) - CYP2B6 G516G>T of P450 (involved in NNRTIs metabolism)
We are currently developing further genetic tests to detect allelic variants not only involved in drug pharmacokinetics but in HIV pathogenicity and immune response.
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Aggiornato il 01 dicembre 2017 |
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