Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy.
BACKGROUND
Plasma concentrations of tenofovir increase when the drug is coadministered with some ritonavir-boosted protease inhibitors (PI/r). We hypothesized that tenofovir disoproxil fumarate (TDF)-treated patients taking PI/r-based regimens would have a greater decline in renal function than patients receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy.


METHODS
We compared the estimated decline in renal function among 146 human immunodeficiency virus type 1 (HIV-1)-infected patients receiving a TDF+PI/r- (n = 51), TDF+NNRTI- (n = 29), or non-TDF-containing (n = 66) regimen. Plasma tenofovir concentrations were measured at study week 2, and rates of creatinine clearance (CrCl) were estimated using the Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) equations. Mixed-effects models were used to analyze regimen type and tenofovir concentration as predictors of change in CrCl from baseline to weeks 24 and 48.


RESULTS
Decreases in C-G estimates of CrCl were not significantly different among the 3 groups during the first 24 weeks of therapy. However, in adjusted analyses, patients receiving TDF+PI/r had a greater rate of decline in CrCl than did the TDF+NNRTI group (for C-G, -13.9 vs. -6.2 mL/min/year [P = .03]; for MDRD, -14.7 vs. -4.5 mL/min/1.73 m(2)/year [P = .02]). Among TDF-treated patients, tenofovir plasma concentration was not associated with CrCl over time.


CONCLUSIONS
Treatment with TDF and PI/r was associated with greater declines in renal function over 48 weeks compared with TDF+NNRTI-based regimens.
Goicoechea
Miguel
M
Antiviral Research Center, University of California, San Diego, 150 W. Washington St., Ste. 100, San Diego, CA 92103, USA. mgoicoechea@ucsd.edu
Liu
Shanshan
S
Best
Brookie
B
Sun
Shelly
S
Jain
Sonia
S
Kemper
Carol
C
Witt
Mallory
M
Diamond
Catherine
C
Haubrich
Richard
R
Louie
Stan
S
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000145:classification; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects; D063065:Organophosphonates / Q000009:adverse effects*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000145:classification; D000068698:Tenofovir; D013995:Time
D017320:HIV Protease Inhibitors; D009705:Nucleosides; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine