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

Am J Kidney Dis. 2016 Oct;68(4):571-581. doi: 10.1053/j.ajkd.2016.03.430. Epub 2016 Jun 8.


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.

Keywords: 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).

Publication types

  • Multicenter Study

MeSH terms

  • Alpha-Globulins / urine*
  • Anti-HIV Agents / adverse effects*
  • Cohort Studies
  • Cross-Sectional Studies
  • HIV Infections / drug therapy*
  • HIV Infections / urine*
  • Humans
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / physiopathology
  • Male
  • Middle Aged
  • Tenofovir / adverse effects*


  • Alpha-Globulins
  • Anti-HIV Agents
  • alpha-1-microglobulin
  • Tenofovir