HIV Infection, Tenofovir, and Urine α1-Microglobulin: A Cross-sectional Analysis in the Multicenter AIDS Cohort Study.
BACKGROUND
Tenofovir disoproxil fumarate (TDF) can cause proximal tubular damage and chronic kidney disease in human immunodeficiency virus (HIV)-infected individuals. Urine α1-microglobulin (A1M), a low-molecular-weight protein indicative of proximal tubular dysfunction, may enable earlier detection of TDF-associated tubular toxicity.


METHODS
Cross-sectional.


METHODS
883 HIV-infected and 350 -uninfected men enrolled in the Multicenter AIDS Cohort Study.


METHODS
HIV infection and TDF exposure.


RESULTS
Urine A1M level.


RESULTS
Urine A1M was detectable in 737 (83%) HIV-infected and 202 (58%) -uninfected men (P<0.001). Among HIV-infected participants, 573 (65%) were current TDF users and 112 (13%) were past TDF users. After multivariable adjustment including demographics, traditional kidney disease risk factors, and estimated glomerular filtration rate, HIV infection was associated with 136% (95% CI, 104%-173%) higher urine A1M levels and 1.5-fold (95% CI, 1.3- to 1.6-fold) prevalence of detectable A1M. When participants were stratified by TDF exposure, HIV infection was associated with higher adjusted A1M levels, by 164% (95% CI, 127%-208%) among current users, 124% (95% CI, 78%-183%) among past users, and 76% (95% CI, 45%-115%) among never users. Among HIV-infected participants, each year of cumulative TDF exposure was associated with 7.6% (95% CI, 5.4%-9.9%) higher A1M levels in fully adjusted models, a 4-fold effect size relative to advancing age (1.8% [95% CI, 0.9%-2.7%] per year). Each year since TDF treatment discontinuation was associated with 4.9% (95% CI, -9.4%--0.2%) lower A1M levels among past users.


CONCLUSIONS
Results may not be generalizable to women.


CONCLUSIONS
HIV-infected men had higher urine A1M levels compared with HIV-uninfected men. Among HIV-infected men, cumulative TDF exposure was associated with incrementally higher A1M levels, whereas time since TDF treatment discontinuation was associated with progressively lower A1M levels. Urine A1M appears to be a promising biomarker for detecting and monitoring TDF-associated tubular toxicity.
Department of Medicine, San Francisco VA Medical Center, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA. Electronic address: vasantha.jotwani@ucsf.edu.
Vasantha
V
Jotwani
Department of Medicine, San Francisco VA Medical Center, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
Rebecca
R
Scherzer
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
Michelle M
MM
Estrella
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Lisa P
LP
Jacobson
Division of HIV Medicine, Department of Medicine, Harbor-UCLA Medical Center and the Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA.
Mallory D
MD
Witt
Division of Infectious Diseases, Department of Medicine, Northwestern University, Chicago, IL.
Frank J
FJ
Palella
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Bernard
B
Macatangay
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Michael
M
Bennett
Section of Nephrology, Department of Medicine, Yale University, New Haven, CT; Program of Applied Translational Research, Yale University, New Haven, CT.
Chirag R
CR
Parikh
Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA.
Joachim H
JH
Ix
Department of Medicine, San Francisco VA Medical Center, San Francisco, CA; Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, CA.
Michael G
MG
Shlipak
D000510:Alpha-Globulins / Q000652:urine*; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000009:adverse effects*
D000510:Alpha-Globulins; D019380:Anti-HIV Agents; C016001:alpha-1-microglobulin; D000068698:Tenofovir
HIV infection; Multicenter AIDS Cohort Study (MACS); Tenofovir disoproxil fumarate (TDF); antiretroviral (ARV) medication; biomarker; kidney damage; nephrotoxicity; proximal tubular dysfunction; tubular toxicity; urine α(1)-microglobulin (A1M)