medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.1234/XXXX-XXXX-2013-2-13-17medgen-38Research ArticleНАУЧНЫЕ ОБЗОРЫREVIEWВЛИЯНИЕ ГЕНЕТИЧЕСКИХ ФАКТОРОВ ЧЕЛОВЕКА НА ВЫСОКОАКТИВНУЮ АНТИРЕТРОВИРУСНУЮ ТЕРАПИЮ (ВААРТ)THE INFLUENCE OF HUMAN GENETIC FACTORS ON HAARTТумановА. С.TumanovA. S.desep@mail.ruФГБУ «НИИ вирусологии им. Д.И. Ивановского» М3 РФРоссияThe D.I. Ivanovsky Institute of Virology of The Min istry of Health of The Russian FederationRussian Federation2013231220151221317Copyright © Туманов А.С., 20152015Туманов А.С.Tumanov A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/38

Изучение генетических факторов человека, ассоциированных с эффективностью лечения ВИЧ-инфекции, является важным направлением в борьбе с нею и СПИДом. За последние два десятилетия было обнаружено много ассоциаций между различными аллельными вариантами генов человека и эффективностью антиретровирусной терапии (APT) ВИЧ-инфекции. Особенный интерес для исследователей представляют аллельные варианты генов, ассоциированные с тяжёлыми осложнениями, возникающими при применении APT. Многие из изученных ассоциаций требуют проведения подтверждающих и уточняющих исследований. В данной статье проведён обзор генетических факторов, дающий ключ к пониманию возможности повышения эффективности применения APT для ВИЧ-инфицированных пациентов.

 

The review discusses role of human genetic factors in efficiency and complications of highly active antiretrovirus therapy (HAART). Genetic polymorphism of cytochrom P450 and multidrug resistance systems (specifically, CYP2B6 and MDR1/MRP1/P-gp, respectively) affects intracellular concentration of numerous antiretroviral drugs (AD) that may explain differences in clin i cal efficacy of HAART. Genetic background might also impact in rate of miscellaneous complications in patients receiving HAART. Thus hypersensitivity to reverse transcriptase inhibitors has been shown to be dependent on the presence of TNF alpha cytokine gene variant 308A or some alleles of HLA class I (HLA-B*5701,HLA-B*3505, HLA-B*14, HLA-Cw*4, HLA-Cw*8) or class II (HLA-DRB1*0101) loci. Protection from lipodistrophia that represents serious complication of HAART depends on presence of parficu i ar ali eles of polymorphic cytokine genes IL-1, IL-18 and TNF beta. Vice versa, susceptibility to enhanced trigleciride level foli owi ng HAART is associated with polymorphic alleles of APOC3, ARb2, ARb3, HFE, LPIN1 and POLG loci whereas increased risk of neuropathy is associated with genetic variants G516T and C983T of CYP2B6 gene. Various complications like hyperbilirubinemia,neutropenia and astma were found to be associated with UGT1A1*28 that controls small lipophilic molecules, A1203A (rs11568695) of MRP4and HLA-A*68, respectively. Data clearly demonstrates the need in personali zation through genetic profili ng in HAART to increase its efficiency and decrease the rate of complications.

 

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The authors declare that there are no conflicts of interest present.