ABCC2*1C and plasma tenofovir concentration are correlated to decreased glomerular filtration rate in patients receiving a tenofovir-containing antiretroviral regimen.
OBJECTIVE
To study the correlations of genetic variants of tenofovir tubular transporters, plasma tenofovir concentrations and clinical factors with decreased glomerular filtration rate in HIV-infected patients who received tenofovir.


METHODS
A total of 117 HIV-1-infected patients were administered antiretroviral therapy with tenofovir/lamivudine/efavirenz. Two single nucleotide polymorphisms (SNPs), ABCC2*1C c.-24C>T and ABCB1*6 c.3435C>T, were genotyped. At week 24, plasma tenofovir concentration at 12 h after drug intake was measured. Serum creatinine and estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease study formula were measured every 24 weeks until 96 weeks.


RESULTS
Overall, mean ± SD age was 37 ± 9 years. Mean ± SD baseline eGFR was 130.3 ± 35.0 mL/min/1.73 m(2). The frequencies of wild-type/heterozygous/homozygous mutants of ABCC2*1C were 57%/39%/4% and those of ABCB1*6 were 28%/51%/21%. Mean ± SD plasma tenofovir concentration at 24 weeks was 105 ± 46 ng/mL. At week 48, m-ean ± SD eGFR of ABCC2*1C CC versus CT/TT was 96 versus 108 mL/min (P = 0.005) and m-ean ± SD eGFR of ABCB1*6 CC versus CT/TT was 106 versus 99 mL/min (P = 0.157). Mean ± SD tenofovir concentration in ABCC2*1C genotype CC versus CT/TT was 113 ± 47 versus 93 ± 44 ng/mL, respectively (P = 0.018). By multivariate analysis I, decreased eGFR at week 48 was correlated to ABCC2*1C genotype CC (P = 0.001), low eGFR at baseline (P = 0.006) and older age (P = 0.048). By multivariate analysis II, decreased eGFR at week 48 was correlated to high plasma tenofovir concentration (P = 0.001) and low eGFR at baseline (P = 0.019).


CONCLUSIONS
HIV-infected patients who carry ABCC2*1C genotype CC at position -24 or have high plasma tenofovir concentration are at risk of decreased glomerular filtration rate.
Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi 11000, Thailand drweerawat@hotmail.com.
Weerawat
W
Manosuthi
Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Chonlaphat
C
Sukasem
Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi 11000, Thailand.
Supeda
S
Thongyen
Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi 11000, Thailand.
Samruay
S
Nilkamhang
Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
Somnuek
S
Sungkanuparph
D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D063065:Organophosphonates / Q000097:blood* / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000627:therapeutic use; D000068698:Tenofovir
D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003404:Creatinine; D003521:Cyclopropanes; D019259:Lamivudine; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; C000715087:ABCC2 protein, human; C098320:efavirenz
HIV; Thailand; kidney; transporter