UTICAJ POJEDINAČNIH NUKLEOTIDNIH POLIMORFIZAMA NA TERAPIJSKU EFIKANOST ANTIRETROVIRUSNIH LEKOVA
Sažetak
Uvod: Dostupnost kombinovane antiretrovirusne terapije (cART) značajno je promenila prognozu infekcije virusom humane imunodeficijencije (HIV). Kako bi se kontrolisala infekcija, pacijenti hronično uzimaju različite grupe antiretrovirusnih lekova, što dovodi do povećane incidence neželjenih dejstva lekova, kao i potencijalnih interakcija sa drugim primenjenim terapijskim tretmanima. Većina dostupnih antiretrovirusnih lekova se metaboliše preko enzima citohroma P450 a izlučuje putem različitih transportnih proteina, koji mogu pokazivati brojne genetske promene. Pojedinačni nukleotidni polimorfizmi su predmet instraživanja u mnogim oblastima, uključujući i HIV infekciju. Od posebnog su značaja polimorfizmi gena koji kodiraju metaboličke enzime i transportere.
Cilj: Cilj ovog istraživanja bio je pregled i analiza najčešćih polimorfizama gena koji kodiraju metaboličke enzime i transportere bitne za farmakokinetiku antiretrovirusnih lekova.
Metod rada: Pretraživanjem Pub Med i Medline baza podataka, za period od 1998. do 2022. Godine uz adekvatne ključne reči poput „cytochrome”, „antiretroviral”, „genotype”, „polymorphism”, „pharmacogenetic”, „pharmacogenomic”, „pharmacokinetic”, „variant”, „single nucleotide polimorphis“, u kombinaciji sa „human immunodeficiency virus“ i „acquired immunodeficiency syndrome“ uradjen je pregled i analiza literature.
Rezultat analize: Klinički najvažniji polimorfizmi koji utiču na terapijsku efikasnost antiretrovirusnih lekova su HLA-B ∗5701, polimorfizmi CYP2B6 koji su povezani sa visokom koncentracijom efavirenza u plazmi i UGT1A1 ∗6 i ∗28 koji su odgovorni za individualne varijacije u farmakokinetici dolutegravira.
Zaključak: Pojedinačni nukleotidni polimorfizmi, zajedno sa drugim faktorima kao što su pol, komorbiditeti, starost pacijenta i istovremene infekcije, mogu značajno uticati na terapijski odgovor. Razumevanje ovih faktora od ključne je važnosti za personalizovan pristup lečenju HIV infekcije i optimizaciju terapijskih rezultata.
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