title: ABCB1 and ABCC1 variants associated with virological failure of first-line protease inhibitors antiretroviral regimens in Northeast Brazil patients.
abstract: The present study aims at evaluating the association between seven single nucleotide polymorphisms (SNPs) in five genes involved on antiretroviral pharmacokinetic pathways and virological failure in first line highly active antiretroviral therapy. Seven candidate polymorphisms (rs3842 and rs1045642 in ABCB1, rs212091 and rs3743527 in ABCC1, rs3745274 in CYP2B6, rs628031 in SLC22A1 and rs1517618 in SLCO3A1) were evaluated if they were associated with virological failure through logistic regression analysis. The study design was a retrospective cohort, analyzing 187 patients from Recife metropolitan region (Pernambuco, Brazil): among these 160 obtained complete suppression of HIV-1 replication (responders) and were compared to 27 non-responders, which underwent virological failure. There was no association between CYP2B6, SLC22A1, and SLCO3A1 SNPs and virological failure. Using logistic regression analysis, a significant association was detected between rs1045642 (3435C>T, ABCB1) and rs212091 (198217T>C; 3'-UTR, ABCC1) with virological failure of first-line antiretroviral regimens containing protease inhibitors, when controlled by clinical factors, such as sex, age and race. The present results could contribute to unravel the influence of genetic background in anti-HIV-1 therapy outcome and help in treatment personalization of Northeast Brazil HIV infected patients.
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, PE, Brazil; Laboratory of Immunopatology Keizo Asami (LIKA), Federal University of Pernambuco, Recife, PE, Brazil.
authors.forename: Antonio V C
authors.initials: AV
authors.lastname: Coelho
authors.forename: Suedja P S
authors.initials: SP
authors.lastname: Silva
authors.forename: Luiz C A
authors.initials: LC
authors.lastname: de Alencar
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stocco
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Lucas A C
authors.initials: LA
authors.lastname: Brandão
authors.forename: Rafael L
authors.initials: RL
authors.lastname: Guimarães
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017320:HIV Protease Inhibitors; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1
keywords: HIV-1; pharmacodynamics; pharmacogenetics