Renal function of participants in the Bangkok tenofovir study--Thailand, 2005-2012.
BACKGROUND
Tenofovir disoproxil fumarate (tenofovir) has been associated with renal dysfunction in people infected with human immunodeficiency virus (HIV) receiving combination antiretroviral therapy. We reviewed data from an HIV preexposure prophylaxis trial to determine if tenofovir use was associated with changes in renal function in an HIV-uninfected population.


METHODS
During the trial, 2413 HIV-uninfected people who inject drugs were randomized to receive tenofovir or placebo. We assessed the renal function of trial participants with the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using t tests for cross-sectional analysis and linear regression for longitudinal analysis.


RESULTS
Creatinine clearance and glomerular filtration rate (GFR) results were lower at 24, 36, 48, and 60 months in the tenofovir group compared with the placebo group. Results declined more in the tenofovir group than in the placebo group during follow-up using the Cockcroft-Gault (P < .001) and CKD-EPI (P = .007) equations, but not MDRD (P = .12). Creatinine clearance measured when study drug was stopped was lower in the tenofovir group than the placebo group (P < .001), but the difference resolved when tested a median of 20 months later (P = .12).


CONCLUSIONS
We found small but significant decreases in cross-sectional measures of creatinine clearance and GFR in the tenofovir group compared with the placebo group and modest differences in downward trends in longitudinal analysis using the Cockcroft-Gault and CKD-EPI equations. These results suggest that with baseline assessments of renal function and routine monitoring of creatinine clearance during follow-up, tenofovir can be used safely for HIV preexposure prophylaxis. Clinical Trials Registration. NCT00119106.
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi Centers for Disease Control and Prevention, Atlanta, Georgia.
Michael
M
Martin
Bangkok Tenofovir Study Group.
Suphak
S
Vanichseni
Bangkok Tenofovir Study Group.
Pravan
P
Suntharasamai
Bangkok Tenofovir Study Group.
Udomsak
U
Sangkum
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi.
Philip A
PA
Mock
Centers for Disease Control and Prevention, Atlanta, Georgia.
Roman J
RJ
Gvetadze
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi Centers for Disease Control and Prevention, Atlanta, Georgia.
Marcel E
ME
Curlin
Bangkok Metropolitan Administration.
Manoj
M
Leethochawalit
Bangkok Metropolitan Administration.
Sithisat
S
Chiamwongpaet
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi.
Thitima
T
Cherdtrakulkiat
Bangkok Metropolitan Administration.
Rapeepan
R
Anekvorapong
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi.
Wanna
W
Leelawiwat
Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi.
Nartlada
N
Chantharojwong
Centers for Disease Control and Prevention, Atlanta, Georgia.
Janet M
JM
McNicholl
Centers for Disease Control and Prevention, Atlanta, Georgia.
Lynn A
LA
Paxton
Thailand Ministry of Public Health, Nonthaburi.
Somyot
S
Kittimunkong
Bangkok Tenofovir Study Group.
Kachit
K
Choopanya
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D007677:Kidney Function Tests; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D065129:Pre-Exposure Prophylaxis; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use*; D013785:Thailand
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D003404:Creatinine
creatinine clearance; glomerular filtration rate; tenofovir disoproxil fumarate