The 3-year renal safety of a tenofovir disoproxil fumarate vs. a thymidine analogue-containing regimen in antiretroviral-naive patients.
BACKGROUND
Cases of renal dysfunction in patients receiving tenofovir disoproxil fumarate (TDF) have been reported. We analyzed the renal safety of TDF compared with thymidine analogue-containing (control) regimens through 144 weeks from two clinical trials in antiretroviral-naive HIV-infected patients.


METHODS
We evaluated the changes in renal parameters in 1111 patients (TDF, n = 556; control, n = 555) who were enrolled in two randomized, controlled trials (Studies 903 and 934) comparing TDF vs. either stavudine or zidovudine in combination with efavirenz and either lamivudine or emtricitabine. The studies included patients with serum creatinine less than 1.5 mg/dl, serum phosphorus at least 2.2 mg/dl and estimated glomerular filtration rate by Cockcroft-Gault at least 60 and at least 50 ml/min at screening.


RESULTS
Baseline characteristics were similar between groups. No patient discontinued due to renal abnormalities in the TDF arm. Through 144 weeks, the proportion of patients who experienced confirmed abnormalities in serum creatinine (>1.5 mg/dl) or serum phosphorus (<2.0 mg/dl) was less than 1% in both groups; a similar proportion of patients experienced urine proteinuria at least 100 mg/dl (TDF, 5%; control, 6%). The median change from baseline to week 144 in glomerular filtration rate was -2 and 3 ml/min by Cockcroft-Gault, and -2 and -1 ml/min per 1.73 m by modification of diet in renal disease in the TDF and control groups (P < 0.05), respectively.


CONCLUSIONS
In two randomized, controlled trials, small differences in glomerular filtration rate over time were noted but no clinically relevant renal disease or adverse events were demonstrated in antiretroviral-naive patients treated with TDF through 144 weeks. Additional studies on renal health and renal safety in HIV are important goals for future clinical trials.
Gallant
Joel E
JE
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Winston
Jonathan A
JA
DeJesus
Edwin
E
Pozniak
Anton L
AL
Chen
Shan-Shan
SS
Cheng
Andrew K
AK
Enejosa
Jeffrey V
JV
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology*; D010758:Phosphorus / Q000097:blood; D011507:Proteinuria / Q000139:chemically induced; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D018119:Stavudine / Q000494:pharmacology; D000068698:Tenofovir; D055815:Young Adult; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D010758:Phosphorus; D015215:Zidovudine; D000068698:Tenofovir; D003404:Creatinine; D018119:Stavudine; D000225:Adenine