Wyatt, Christina M.Kitch, DouglasGupta, Samir K.Tierney, CamlinDaar, Eric S.Sax, Paul E.Ha, BelindaMelbourne, KathleenMcComsey, Grace A.AIDS Clinical Trials Group Study A5224s Team2016-03-312016-03-312014-09-01Wyatt, C. M., Kitch, D., Gupta, S. K., Tierney, C., Daar, E. S., Sax, P. E., … McComsey, G. A. (2014). Changes in Proteinuria and Albuminuria with Initiation of Antiretroviral Therapy: Data from a Randomized Trial Comparing Tenofovir Disoproxil Fumarate/Emtricitabine versus Abacavir/Lamivudine. Journal of Acquired Immune Deficiency Syndromes (1999), 67(1), 36–44. http://doi.org/10.1097/QAI.00000000000002451944-7884https://hdl.handle.net/1805/9149BACKGROUND: 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.en-USPublisher PolicyAlbuminuriavirologyAnti-HIV Agentsadministration & dosageHIV Infectionsdrug therapyUrineHIV-1drug effectsProteinuriaArticle