Codice | QDD 157 |
Titolo | COMBINATION VERSUS SEQUENTIAL MONOTHERAPY IN CHRONIC HBV INFECTION: A MATHEMATICAL APPROACH |
Data | 2013-05-31 |
Autore/i | BERTACCHI, D.; ZUCCA, F.; FORESTI, S.; MANGIONI, D.; GORI, A. |
Link | Download full text |
Abstract | Sequential monotherapy is the most widely used therapeutic approach in the treatment
of HBV chronic infection. Unfortunately, under therapy, in some patients the hepatitis virus mutates
and gives rise to variants which are drug resistant. We conjecture that combination therapy is able
to delay drug resistance for a longer time than sequential monotherapy. To study the action of
these two therapeutic approaches in the event of unknown mutations and to explain the emergence
of drug resistance, we propose a stochastic model for the infection within a patient which is treated
with two drugs, either sequentially or contemporaneously, and develops a two-step mutation which
is resistant to both drugs. We study the deterministic approximation of our stochastic model and
give a biological interpretation of its asymptotic behaviour. We compare the time when this new
strain first reaches detectability in the serum viral load. Our results show that the best choice is
to start an early combination therapy, which allows to stay drug-resistance free for a longer time. |
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