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

• Published in: AIDS (London) Vol. 26; no. 11; pp. 1371 - 1385
• Main Authors: MCCOMSEY, Grace A, KITCH, Douglas, SAX, Paul E, DAAR, Eric S, TIERNEY, Camlin, JAHED, Nasreen C, MELBOURNE, Kathleen, HA, Belinda, BROWN, Todd T, BLOOM, Anthony, FEDARKO, Neal
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 17.07.2012
• Subjects: Abacavir; Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - immunology; Adenine - analogs & derivatives; Adenine - pharmacology; Adult; Age; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Atazanavir Sulfate; Benzoxazines - pharmacology; Biological and medical sciences; Biomarkers - blood; C-reactive protein; C-Reactive Protein - drug effects; C-Reactive Protein - metabolism; CD4 antigen; Cell adhesion molecules; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Dideoxynucleosides - pharmacology; Drug Combinations; Efavirenz; Emtricitabine; Female; HIV-1 - metabolism; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Inflammation; Inflammation - blood; Inflammation - immunology; Interleukin 6; Interleukin-6 - blood; Lamivudine; Lamivudine - pharmacology; Male; Medical sciences; nucleoside reverse transcriptase inhibitors; Oligopeptides - pharmacology; Organophosphonates - pharmacology; Pharmacology. Drug treatments; Pyridines - pharmacology; Ritonavir; Ritonavir - pharmacology; RNA; Tenofovir; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - drug effects; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Purine nucleoside; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; C-reactive protein; Acetylenic compound; Ritonavir; inflammation markers; Non nucleoside compound; Nucleotide analog; Efavirenz; interleukin-6; Interleukin 6; Tenofovir; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; C reactive protein; Pyrimidine nucleoside; Emtricitabine; Purine nucleotide; endothelial activation markers; Acyclic nucleotide; Atazanavir; TNF alpha; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; Organic phosphonate; Inflammation; Allosteric inhibitor; Peptidases; Nucleotidyltransferases; Acute phase protein; Tumor necrosis factor; Dideoxynucleoside; Abacavir; Hydrolases; Protease inhibitor
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e328354f4fb

The effect of specific antiretrovirals on inflammation is unclear. 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. 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). 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.