Polymorphisms associated with renal adverse effects of antiretroviral therapy in a Southern Brazilian HIV cohort.
OBJECTIVE
This study evaluated the impact of seven single nucleotide polymorphisms in five candidate genes (ABCB1, ABCC2, ABCC4, SLC22A6, and SLC22A11) in relation to nephrotoxicity associated with highly active antiretroviral therapy (HAART) in HIV-infected individuals.


METHODS
The following single nucleotide polymorphisms were genotyped by real-time PCR: ABCB1 rs1045642, ABCC2 rs717620 and rs2273697, ABCC4 rs1751034 and rs3742106, SLC22A6 rs11568626, and SLC22A11 rs11231809 in 507 HIV-infected patients from the city of Porto Alegre, Southern Brazil, receiving HAART for, at least, 1 year.


RESULTS
From the 507 HIV-infected patients recruited, 19.1% presented a reduction in estimated glomerular filtration rate (eGFR). A total of 16 (3.2%) patients fulfilled the criteria for chronic kidney disease (defined as eGFR<60 ml/min/1.73 m). Individuals carrying at least one T allele of ABCC2 -24 C>T (rs717620) presented lower eGFR than C/C homozygotes (104 ± 22 vs. 108 ± 22 ml/min/1.73 m, independent-samples t-test, P=0.040). In multivariate analysis, the predictors associated with decreased eGFR were time of treatment, tenofovir use, atazanavir/ritonavir use, and carrying one T allele of ABCC2 -24 C>T.


CONCLUSIONS
Our data support the importance of genetic factors in the etiology of nephrotoxicity in patients treated with HAART. Studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.
aGraduate Program in Pathology bGraduate Program in Health Sciences, Federal University of Health Sciences of Porto Alegre cHospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Ivete M
IM
da Rocha
Aline S
AS
Gasparotto
Rosmeri K
RK
Lazzaretti
Regina K
RK
Notti
Eduardo
E
Sprinz
Vanessa S
VS
Mattevi
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001938:Brazil; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D027362:Organic Anion Transport Protein 1 / Q000235:genetics; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology
D018435:ATP Binding Cassette Transporter, Subfamily B; D019380:Anti-HIV Agents; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C073492:ABCC4 protein, human; C427207:SLC22A11 protein, human