Baseline levels of soluble CD14 and CD16+56- natural killer cells are negatively associated with response to interferon/ribavirin therapy during HCV-HIV-1 coinfection

Abstract

Disease progression of human immunodeficiency virus type 1 (HIV-1) is associated with immune activation. Activation indices are higher during coinfection of hepatitis C virus (HCV) and HIV. The effect of immune activation on interferon α (IFN-α) therapy response is unknown. We evaluated soluble CD14 (sCD14) and natural killer (NK)-cell subsets at baseline, and during pegIFN-α2a/ribavirin therapy in HCV-HIV coinfection. The sCD14 level increased during therapy. Baseline sCD14 positively correlated with baseline HCV level and CD16(+)56(-) NK-cell frequency, and both sCD14 and CD16(+)56(-) NK cells correlated negatively with magnitude of HCV decline. IL28B genotype was associated with therapy response but not sCD14 or CD16(+)56(-) NK frequency. Markers of innate immune activation predict poor host response to IFN-α-based HCV therapy during HCV-HIV coinfection.

Figure 1.

Plasma soluble CD14 (sCD14) increases during pegylated interferon-α/ribavirin (pegIFN/RBV) killer (NK)–cell frequency. A, Plasma sCD14 level was measured at baseline, week 12, and week 24 of pegIFN/RBV therapy (n = 19, all HCV genotypes). B, C, Baseline plasma sCD14 level (B) and CD3–14-19-16⁺56⁻ NK-cell frequency (C)in relation to week 4 (n = 14 for sCD14 and n = 19 for CD16⁺CD56⁻ NK), week 12 (n = 14 for sCD14, and n = 20 for CD16⁺CD56⁻ NK), and week 24 (n = 13 for sCD14 and n = 19 for CD16⁺CD56⁻ NK) HCV genotype-1 viral decline magnitude.

Figure 2.

Pairwise comparisons for hepatitis C virus (HCV) genotype 1 virologic response status. A, Plasma sCD14 at baseline (week 0) and week 12 is plotted by virologic response status (rapid virologic response [RVR], early virologic response [EVR], complete EVR [cEVR], and sustained virologic response [SVR]). B, Week 0 CD16⁺56⁻ natural killer (NK) frequency by virologic response status. Box plots represent median, interquartile range, minimum, and maximum. P < .1 is shown.