A comparative study of the renal safety of tenafovir and stavudine in Kenyatta National Hospital
Background: Tenofovir is a nucleotide reverse transcriptase inhibitor that has been suggested to be a potent and safer alternative to both stavudine (D4T)- and zidovudine-based first-line regimens for the treatment of HIV infection. The current WHO guidelines strongly recommend tenofovir disoproxil fumarate (TDF) as first-line treatment for antiretroviral therapy (ART)-naive individuals. Despite this, tenofovir has been reported to cause severe renal adverse events and this could limit its use to selected patient populations. Objective: To assess the incidence of tenofovir-induced nephrotoxicity and to identify risk factors for this adverse event using stavudine as a comparator drug. Methodology: This was a retrospective cohort study carried out at the Comprehensive Care Centre of Kenyatta National Hospital. The study population was HIV -infected adult patients on any TDF-based and D4T-based regimens seen between January 2008 to March 2010. A working sample size of 396 patients selected from a list of patients who met the inclusion criteria. Data collected was entered into and analysed using SPSS (version 12.0) and STAT A (version 9.0) statistical software. Results: The incidence rate (IR) of nephrotoxicity (creatinine clearance <60 rnL/min) was higher in patients initiated on TDF than in patients initiated on low dose D4T (9.0 cases per 1000 person-months and 4.0 cases per 1000 person-months respectively) giving an incidence rate ratio (IRR) of 2.25. Patients who had switched from D4T to TDF had lipodystrophy (52.7%) and peripheral neuropathy (27.3%) toxicities as the most common reason for change . Age greater than 40 years (HR=2.88; 95% CI: 1.56 - 5.34; p=O.OOl), weight less than 65 kilograms (HR=5.04; 95% CI: 2.06 - 12.32; p<O.OOl), use of Efavirenz regimen base (HR=2.47; 95% CI: 1.24 - 4.94; p=0.010) and use of Amphotericin B (HR=20.68; 95% CI: 4.05 - 105.70; p<O.OOl) were found to be the independent risk factors of nephrotoxicity. There was no significant difference in median change in creatinine clearance between the treatment groups with time. Frequency of monitoring was more intense in patients who had abnormai renal function at baseline or had risk factors for nephrotoxicity. Conclusion: The incidence for nephrotoxicity due to 1 st line tenofovir-based HAART is low in the observed cohort but still much higher than that attributed to stavudine-based therapy. There is need for close monitoring especially in such high risk groups as the elderly, underweight patients and those on nephrotoxic drugs. The association between EFV and nephrotoxicity requires further investigation.