 Background : In Thailand, combination of tenofovir disoproxil fumarate (TDF) with ritonavir-boosted lopinavir (LPV/r) or nonnucleoside reverse-transcriptase inhibitor (NNRTI) are commonly used for HIV-treatment failure patients. Decreasing of creatinine clearance (CrCl) is one of the most concerned adverse events for TDF. This study aimed to determine the changes in CrCl after two years of TDF combination regimen and compare between LPV/r and NNRTI. Study design : Retrospective cohort studyMethods : Review data of CrCl and recalculated with MDRD equation from patients in HIV clinic during 1st January 2010 to 31st December 2014 who received TDF combination regimen for two years.Results : Of 135 patients receiving TDF, there were 39 cases (28.9%) combined with LPV/r and 96 (71.1%) combined with NNRTI (nevirapine or efavirenz). The CrCl before and after two years of TDF use were 92.72 mL/min/1.73m2 and 81.75 mL/min/1.73m2, respectively (p<0.001). TDF+LPV/r group had the most decrease of CrCl (15.36 mL/min/1.73m2) and nine in 39 patients (23.1%) decreased CrCl for more than 25 percents. Seventeen in 96 patients in TDF+NNRTI group had decreased CrCl more than 25 percents, representing a relative risk of 1.3 (95%CI 0.6 to 2.7). However, no any patients discontinued from TDF during the study period. Conclusion : There are greater declines in CrCl after two years with TDF+LPV/r compared with TDF+NNRTI regimen but there are no change in clinical outcome. Further study with longer follow up is needed.