title: Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine.
abstract: BACKGROUND
  Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria.
  
  
  METHODS
  We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz.
  
  
  RESULTS
  At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components.
  
  
  CONCLUSIONS
  In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings.
authors.affiliation: *Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; §Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA; ‖Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; ¶ViiV Healthcare, Research Triangle Park, NC; #Gilead Sciences, Foster City, CA; and **Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wyatt
authors.forename: Douglas
authors.initials: D
authors.lastname: Kitch
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Belinda
authors.initials: B
authors.lastname: Ha
authors.forename: Kathleen
authors.initials: K
authors.lastname: Melbourne
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000419:Albuminuria / Q000821:virology*; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000008:administration & dosage; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D016014:Linear Models; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage; D011507:Proteinuria / Q000821:virology*; D000068698:Tenofovir; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir