1. www.aids2014.org Abstract No. THPDB0103 1 Genetic and Molecular Biology Laboratory, Hosp.Univ. La Paz-HCIII, Madrid, Spain, 2 Departament of Molecular and Clinical Pharmacology, Univ. Liverpool, UK and 3 Infectious Diseases Department, Hosp. Univ. La Paz-HCIII, Madrid, Spain Alvarez E 1, Owen A 2, Martín Carbonero L 3, Siccardi M 2, Valencia E 2, Moreno V 2, Fernández O 1, Cuenca L 1, and Rodríguez-Nóvoa S 1 Background:  Variability in the characteristics and severity of KTD might be influenced by host genetic factors.  Kidney tubular dysfunction (KTD) has been associated with long term TDF exposure, urine phosphate wasting being one of the earliest clinical manifestations of KTD. Polymorphisms in SLC34A1 and ABCC2 genes are related with altered renal tubular function in HIV patients receiving Tenofovir. To examine the association between host single nucleotide polymorphisms (SNPs) and abnormal tubular reabsorption of phosphate (TRP) Objective

2. www.aids2014.org Methods:  Retrospective case-control study.  Accordingly with TRP value: cases TRP 0.82  20 SNPS were studied in 6 genes potentially affecting TDF-PK and Phosphate tubular reabsorption.  All SNPs were analyzed using Taqman probes. Haplotypes were constructed using PHASE software Results (I)  96 HIV patients were included: 39 cases and 57 controls  Cases were longer exposed to TDF: 43 vs 24 months, p=0.01 OAT4 TFV OAT3 OAT1 TFV Urine Blood Renal Tubular Cell NPT2a TFV Pi MRP2 Intestinal lumen Enterocyte P-gp TDF TFV P-gp TDF MPR4

3. www.aids2014.org CCCT/TT Genotype SLC34A1, rs3812036 p =0.03 CCCT/TT Genotype ABCC4, rs899494 p =0.053 Normal TRP Abnormal TRP Results (II)  Single SNP analysis: 30% 54%46% 23%

4. www.aids2014.org P.E, 95% C.Ip Comorbidities (Hypertension, Diabetes)3.9 [1.16-13.08]0.027 TDF exposure (months)1.04 [1.001-1.07]0.045 Haplotype SLC34A1TG+ABBC2-CGTC6.5 [1.67-25.36] 0.007 Adjustement for age, gender, ethnicity, BMI, HIV RNA, CD4+ T-cells, concomitant ARV and other nephrotoxic drugs Monitoring phosphate wasting and screening for genetic polymorphisms could be useful for early identification of patients at higher risk of developing KTD. Conclusion Results (II) Variables independently associated with abnormal TRP Normal TRP Abnormal TRP Haplotype SLC34A1 Haplotype ABCC2 Any OtherTG Any Other CGTC p =0.03p =0.048 28% 54% 28% 48%  Haplotype analysis:

5. www.aids2014.org Thank you!!