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.

Fig. 1. Mean fold change in sICAM, sVCAM, TNF-a, sTNFR-I, and sTNFR-II by Intent-to-Treat Analysis with 95% confidence intervals (CI) for the means at weeks 24 and 96 for the four Treatment Arms

Fig. 2. Mean fold change in hsCRP (panel a) and IL-6 (panel b) by intent-to-treat analysis with 95% confidence intervals (CI) for the means at weeks 24 and 96 by NRTI and NNRTI/PI components, and for the four treatment arms

Week 0 and Week 24 hsCRP for ABC/3TC and TDF/FTC are shown in panel c as distribution by hsCRP (mg/liter) values, with black bars representing median values, and in panel d as distribution by American Heart Association Risk categories. From bottom to top: hsCRP <1 mg/liter (low risk), 1–3 mg/liter (average risk), >3 mg/liter (high risk), and >10 mg/liter.