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

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.

• Authors: 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
• Journal: AIDS (London, England) (AIDS) Vol. 26 Issue 11 Pg. 1371-85 (Jul 17 2012) ISSN: 1473-5571 [Electronic] England
• PMID: 22546988 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Anti-HIV Agents
• Benzoxazines
• Biomarkers
• Cyclopropanes
• Dideoxynucleosides
• Drug Combinations
• Interleukin-6
• Oligopeptides
• Organophosphonates
• Pyridines
• Tumor Necrosis Factor-alpha
• abacavir, lamivudine drug combination
• Deoxycytidine
• Lamivudine
• Atazanavir Sulfate
• C-Reactive Protein
• Tenofovir
• Emtricitabine
• Adenine
• efavirenz
• Ritonavir

Topics

• Acquired Immunodeficiency Syndrome (blood, drug therapy, immunology)
• Adenine (analogs & derivatives, pharmacology)
• Adult
• Alkynes
• Anti-HIV Agents (pharmacology)
• Atazanavir Sulfate
• Benzoxazines (pharmacology)
• Biomarkers (blood)
• C-Reactive Protein (drug effects, metabolism)
• Cyclopropanes
• Deoxycytidine (analogs & derivatives, pharmacology)
• Dideoxynucleosides (pharmacology)
• Drug Combinations
• Emtricitabine
• Female
• HIV-1 (metabolism)
• Humans
• Inflammation (blood, immunology)
• Interleukin-6 (blood)
• Lamivudine (pharmacology)
• Male
• Oligopeptides (pharmacology)
• Organophosphonates (pharmacology)
• Pyridines (pharmacology)
• Ritonavir (pharmacology)
• Tenofovir
• Tumor Necrosis Factor-alpha (blood, drug effects)