Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine.

TitleChanges in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine.
Publication TypeJournal Article
Year of Publication2014
AuthorsWyatt CM, Kitch D, Gupta SK, Tierney C, Daar ES, Sax PE, Ha B, Melbourne K, McComsey GA
Corporate AuthorsAIDS Clinical Trials Group Study A5224s Team
JournalJ Acquir Immune Defic Syndr
Volume67
Issue1
Pagination36-44
Date Published2014 Sep 1
ISSN1944-7884
KeywordsAdenine, Adult, Albuminuria, Anti-HIV Agents, Deoxycytidine, Dideoxynucleosides, Drug Combinations, Emtricitabine, Female, HIV Infections, HIV-1, Humans, Lamivudine, Linear Models, Male, Organophosphonates, Proteinuria, Tenofovir
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.

DOI10.1097/QAI.0000000000000245
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID25117929
PubMed Central IDPMC4134097
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