Study of tenofovir nephrotoxicity while comparing the cases on tenofovir containing tle regimen and their controls on non- tenofovir containing znl regimen at a tertiary care hospital in northern india

Introduction: National AIDS Control Organisation (NACO) recommends either Zidovudine or Tenofovir Disoproxil Fumarate (TDF) as one of the reverse transcriptase inhibitors (RTIs) to be included in the first-line ART regimens- Zidovudine, Nevirapine and Lamivudine regimen (ZNL regimen); and Tenofovir, Lamivudine and Efavirenz regimen (TLE regimen). Tenofovir has been variously documented as a potential agent that can cause nephrotoxicity and bone mineral disease, but, there are conflicting observations about the clear evidence of any Tenofovir-induced nephrotoxicity and related aspects. The current study is aimed to address this issue.
Material and methods: The prospective case-control study was conducted at a NACO and PSACS-approved ART-OPD of Government Medical College & Guru Nanak Dev Hospital, Amritsar on 100 HIV-positive cases, with ages between 18 to 65 years, and with a minimum of more than 6 weeks of duration of treatment; on Tenofovir-based ART (TLE regimen) who were compared with 100 similar HIV-positive patients on non-Tenofovir-based ART (ZNL regimen) serving as their controls. Patients with pre-existing underlying renal disease, diabetes mellitus, hypertension, concomitant use of any nephrotoxic drug, protease inhibitor or steroid therapy for any cause for a duration of more than 3 months were excluded. The cases and controls were compared for age (completed years), duration of treatment with ART (in months), height, weight, BMI, corrected serum calcium, creatinine clearance (estimated using the Cockcroft-Gault equation), CD4 count at initiation of ART, and sex of the study subjects. Renal toxicity TDF was evaluated by tubular proteinuria and reduced creatinine clearance (calculated by Cockcroft-Gault Equation). Data analysis was conducted by using statistical software SPSS Version 16(89) and Excel 10. Statistical significance was evaluated using Students t test and ANOVA.
Results: The comparison of Urine Protein and Creatinine Ratio (UPCR) among cases and controls showed that Odds Ratio was 7.0 (95% CI 1.1 - 50.1) indicating that risk of having an increased UPCR of 0.2 or more was 7 times higher among those HIV-infected patients who were treated with TDF-based ART as compared to those who were treated on non-TDF-based ART.
The analysis of Cr Cl (as estimated by the Cockcroft-Gault equation) among the groups revealed that the cases had significantly lower Cr Cl as compared to controls (Chi Square value: 5.07, p value 0.022).
Subgroup analysis between different treatment duration groups showed that treatment with TDF is provided for 60 months or longer, it would increase UPCR significantly.
Conclusions: Exposure to TDF during treatment of HIV has a role in lowering the creatinine clearance.