HIV Infection, Tenofovir, and Urine α1-Microglobulin: A Cross-sectional Analysis in the Multicenter AIDS Cohort Study

Vasantha Jotwani, Rebecca Scherzer, Michelle M. Estrella, Lisa P. Jacobson, Mallory D. Witt, Frank J. Palella, Bernard Macatangay, Michael Bennett, Chirag R. Parikh, Joachim H. Ix, Michael G. Shlipak

Research output: Contribution to journalArticlepeer-review


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. Study Design Cross-sectional. Setting & Participants 883 HIV-infected and 350 -uninfected men enrolled in the Multicenter AIDS Cohort Study. Predictors HIV infection and TDF exposure. Outcome 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. Limitations 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.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalAmerican Journal of Kidney Diseases
Issue number4
StatePublished - Oct 1 2016


  • 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-microglobulin (A1M)

ASJC Scopus subject areas

  • Nephrology

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