Risk factors for tenofovir renal toxicity: Impact of prior use of stavudine and co-medications among patients on highly active antiretroviral therapy attending comprehensive care clinic at Kenyatta national hospital, Kenya

Abstract

Objective: To evaluate the incidence of and risk factors for nephrotoxicity in HIV patients on tenofovir (TDF)-based antiretroviral regimens.
Design, Setting and Study participants: This was a four-arm retrospective cohort study among 396 adult patients receiving treatment between January 2008 and March 2010 at the Kenyatta National Hospital, Kenya.
Interventions and main outcome measures: Patients were classified as being on TDF- or D4T-based regimens, those who switched therapy and those on other regimens. Serum creatinine levels and renal creatinine clearance were used to monitor renal function.
Results: Baseline prevalence of impaired renal function was 19.9% (95% CI: 16.3 – 24.2), the incidence was 0.5% (95% CI: 0.4 – 0.7) and the cumulative incidence was 13.5%. Patients who switched regimens had the highest cumulative incidence (19.1% (95% CI: 12.3 – 28.5).
The incidence of nephrotoxicity (creatinine clearance < 60 mL/min) was higher in patients on TDF-based regimens (adjusted HR 2.62 (96% CI: 1.01 – 6.79; p= 0.048). Other risk factors were: age above 40 years (adjusted HR 3.07 (95% CI: 1.48 – 6.36; p = 0.002), weight below 65 kilograms (adjusted HR = 7.53 (95% CI: 2.75 – 20.63); p<0.001), WHO HIV/AIDS Stage IV (adjusted HR 4.13 (1.12 –15.27; p = 0.034); hypertension (adjusted HR = 4.56 (0.98 – 21.21; p = 0.053); amphotericin B (adjusted HR 50.07 (6.90 – 363.42); p= 0.001); and opportunistic infections (adjusted HR = 0.40 (0.16 – 0.96); p = 0.042).
Conclusion: Tenofovir nephrotoxicity is exacerbated by concurrent amphotericin B and efavirenz.