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

TitleInflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir.
Publication TypeJournal Article
Year of Publication2012
AuthorsMcComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Melbourne K, Ha B, Brown TT, Bloom A, Fedarko N, Sax PE
JournalAIDS
Volume26
Issue11
Pagination1371-85
Date Published2012 Jul 17
ISSN1473-5571
KeywordsAcquired Immunodeficiency Syndrome, Adenine, Adult, Anti-HIV Agents, Atazanavir Sulfate, Benzoxazines, Biomarkers, C-Reactive Protein, Deoxycytidine, Dideoxynucleosides, Drug Combinations, Emtricitabine, Female, HIV-1, Humans, Inflammation, Interleukin-6, Lamivudine, Male, Oligopeptides, Organophosphonates, Pyridines, Ritonavir, Tenofovir, Tumor Necrosis Factor-alpha
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.

DOI10.1097/QAD.0b013e328354f4fb
Alternate JournalAIDS
PubMed ID22546988
PubMed Central IDPMC3560932
Grant ListAI065348 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
R01 AI065348 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 RR024992 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States