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Clinical predictors of Tenofovir-associated nephrotoxicity in HIV-1-infected patients
Presented by Chelsea Castellano, United States.
C. Castellano1, W. Williams2, T.B. Kepler1, S. Kim1, L. Szczech1, C. Hicks1
1Duke University Medical Center, Durham, United States, 2Ryan White Clinic, Hickory, United Kingdom
Background: Tenofovir (TDF) is an efficacious and widely used antiretroviral agent. Although it is usually well-tolerated, TDF-associated renal toxicity is not uncommon. Clinical predictors of such toxicity are not fully characterized.
Methods: A cohort study of >1500 HIV-infected patients identified 744 who received TDF for >3 months and who had baseline (BL) serum creatinine (Cr) recorded <1 year prior to TDF initiation. TDF-associated nephrotoxicity was defined as doubling of serum Cr and/or Cr >1.4 mg/dL (men) or >1.2 mg/dL (women) while on TDF. Controls were randomly selected from TDF recipients who had no significant change in Cr. Contingency tables and logistic regression were used to determine associations between clinical variables and the development of renal dysfunction.
Results: 56 cases of TDF-associated nephrotoxicity were identified and compared to 74 controls. Significant predictors of developing nephrotoxicity (odds ratio [95% confidence intervals]) included: previous protease inhibitor (PI) use (OR 2.51 [1.21, 5.21]), chronic pain (as marker of potential NSAID use) (OR 3.27 [1.22, 8.77]); concurrent PI use (OR 3.88 [1.74, 8.64]); hypertension (OR 5.03 [2.34, 10.8]); medical co-morbidities (OR 5.78 [2.61, 12.77]); and concurrent nephrotoxic medications (OR 25.47 [8.81, 73.67]. Higher BL Cr and Medicare/Medicaid insurance were also associated with greater risk. Diminished risk was present when TDF was used as part of an initial regimen (OR 0.23 [0.07, 0.716]) and with concurrent NNRTI use (OR 0.29 [0.14, 0.599]). When both hypertension and nephrotoxic drug use were present, 25/25 (100%) TDF recipients experienced nephrotoxicity; when both were absent, only 1/39 (3%) experienced nephrotoxicity.
Conclusions: Clinical risk factors for significant TDF-associated nephrotoxicity are readily identifiable. TDF use should be avoided in patients with hypertension requiring other nephrotoxic drugs, especially if given with a PI. Use as part of initial NNRTI-based therapy is low risk for nephrotoxicity.
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