Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir

Grace A. McComsey, Douglas Kitch, Eric S. Daar, Camlin Tierney, Nasreen C. Jahed, Kathleen Melbourne, Belinda Ha, Todd T. Brown, Anthony Bloom, Neal Fedarko, Paul E. Sax

Research output: Contribution to journalArticle

Abstract

Background: The effect of specific antiretrovirals on inflammation is unclear. Methods: A5224s was a substudy of A5202, which randomized HIV-infected treatment-naïve patients to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir/ritonavir (ATV/r) in a factorial design. Our analysis compared changes in inflammation markers from baseline to week 24 between ABC/3TC and TDF/FTC. Secondary analyses included changes at week 96 and comparisons of EFV vs. ATV/r. Results: Analyses included 244 patients (85% male, 48% white non-Hispanic), median age 39 years, HIV-1 RNA 4.6 log10 copies/ml, CD4 240 cells/μl. TNF-α, soluble receptors of TNF-α (sTNFR)-I and II, soluble vascular cellular adhesion molecule (sVCAM)-1 and soluble intercellular adhesion molecule (sICAM)-1 decreased significantly at weeks 24 and 96, without significant differences between components (P≥ 0.44). At week 24, ABC/3TC had a greater high-sensitivity C-reactive protein (hsCRP) mean fold change than TDF/FTC {1.43 vs. 0.88, estimated mean fold change percentage difference [Δ] 61.5% [95% confidence interval (CI) 13.6%, 129.5%]; P = 0.008}. Similar results were seen at week 96 (P = 0.021). At week 24 (but not 96), EFV had a greater hsCRP mean fold change than ATV/r [1.41 vs. 0.88; Δ = 60.2% (12.6%, 127.7%); P = 0.009]. IL-6 decreased significantly at week 24 with TDF/FTC but not with ABC/3TC (between-components P = 0.019). At week 96, IL-6 decreased significantly in both nucleoside reverse transcriptase inhibitor components (between-components P = 0.11). IL-6 changes were not significantly different between ATV/r and EFV at either time point (P≥ 0.89). Conclusions: Soluble TNF-receptors and adhesion molecules decreased following treatment initiation and did not differ by regimens. Differences were seen on hsCRP and IL-6 changes with ABC/3TC vs. TDF/FTC and on hsCRP with EFV vs. ATV/r.

Original languageEnglish (US)
Pages (from-to)1371-1385
Number of pages15
JournalAIDS
Volume26
Issue number11
DOIs
StatePublished - Jul 17 2012

Keywords

  • C-reactive protein
  • TNF alpha
  • abacavir
  • endothelial activation markers
  • inflammation markers
  • interleukin-6

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    McComsey, G. A., Kitch, D., Daar, E. S., Tierney, C., Jahed, N. C., Melbourne, K., Ha, B., Brown, T. T., Bloom, A., Fedarko, N., & Sax, P. E. (2012). Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir. AIDS, 26(11), 1371-1385. https://doi.org/10.1097/QAD.0b013e328354f4fb