Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients.
OBJECTIVE
To better characterize the long-term effects of tenofovir on renal function in a large managed care organization.


METHODS
We performed a retrospective cohort analysis in Kaiser Permanente for years 2002 to 2005 comparing renal function among antiretroviral naïve patients initiating a tenofovir-containing regimen (964 patients) or tenofovir-sparing regimens (683 patients). We evaluated glomerular filtration rate (GFR, [Modification of Diet in Renal Disease equation]), serum creatinine, and the development of renal proximal tubular dysfunction. We report multivariable hazard ratios (HR, Cox modeling) and linear outcomes (repeated measures) with predictors retained if P < 0.10 (backward selection). Potential predictor variables included in multivariate models were age, sex, Black race, baseline laboratories (including CD4 count), history of diabetes mellitus, hypertension, malignancy, hepatitis, and concurrent medications.


RESULTS
Overall, tenofovir-exposed patients had a larger relative decline in GFR through 104 weeks (-7.6 mL/min/1.73 m(2) relative to tenofovir-sparing, P < 0.001); the degree of the difference varied by baseline GFR, with the greatest effect seen in those patients with GFR greater than 80 mL/min/1.73 m(2). Tenofovir-exposed patients had greater development of proximal tubular dysfunction over time (at 52 wk: HR(adjusted) = 1.95 [P = 0.01] and at 104 wk: HR(adjusted) = 5.23 [P = 0.0004]) and had greater risk of medication discontinuation (HR(adjusted) = 1.21, P = 0.02), especially as renal function worsened. Viral control and CD4 count changes were similar between the two groups.


CONCLUSIONS
Tenofovir is associated with greater effect on decline in renal function and a higher risk of proximal tubular dysfunction in antiretroviral naïve patients initiating antiretroviral therapy.
HIV Initiative, Kaiser Permanente, 2000 Broadway Oakland, CA 94612, USA. michael.horberg@kp.org
Michael
M
Horberg
Beth
B
Tang
William
W
Towner
Michael
M
Silverberg
Susan
S
Bersoff-Matcha
Leo
L
Hurley
Joseph
J
Chang
Jackie
J
Blank
Charles
C
Quesenberry
Daniel
D
Klein
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005198:Fanconi Syndrome / Q000150:complications* / Q000378:metabolism / Q000821:virology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine