The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of women

Abstract

Objective: HIV causes inflammation that can be at least partially corrected by HAART. To determine the qualitative and quantitative nature of cytokine perturbation, we compared cytokine patterns in three HIV clinical groups, including HAART responders (HAART), untreated HIV noncontrollers, and HIV-uninfected (NEG).

Methods: Multiplex assays were used to measure 32 cytokines in a cross-sectional study of participants in the Women's Interagency HIV Study. Participants from three groups were included: HAART (n = 17), noncontrollers (n = 14), and HIV NEG (n = 17).

Results: Several cytokines and chemokines showed significant differences between noncontrollers and NEG participants, including elevated interferon gamma-induced 10 (IP-10) and tumor necrosis factor-α (TNF-α) and decreased interleukin-12(p40) [IL-12(p40)], IL-15, and fibroblast growth factor-2 (FGF-2) in noncontroller participants. Biomarker levels among HAART women more closely resembled the NEG, with the exception of TNF-α and FGF-2. Secondary analyses of the combined HAART and noncontroller groups revealed that IP-10 showed a strong, positive correlation with viral load and negative correlation with CD4(+) T-cell counts. The growth factors vascular endothelial growth factor, epidermal growth factor, and FGF-2 all showed a positive correlation with increased CD4(+) T-cell counts.

Conclusion: Untreated, progressive HIV infection was associated with decreased serum levels of cytokines important in T-cell homeostasis (IL-15) and T-cell phenotype determination (IL-12), and increased levels of innate inflammatory mediators such as IP-10 and TNF-α. HAART was associated with cytokine profiles that more closely resembled those of HIV-uninfected women. The distinctive pattern of cytokine levels in the three study groups may provide insights into HIV pathogenesis, and responses to therapy.

Figure 1. Cytokine concentration by clinical group

Cytokine levels for each of the analytes showing significant differences between groups are shown. Horizontal bar represents mean level, with error bars denoting the standard error of the mean. * p<0.05, ** p<0.01, *** p<0.001.

Figure 2. Cytokine correlation with HIV plasma viral load and CD4+ T cell count

(a) Plots show log(cytokine level) vs. log(viral load) or (b) log(cytokine level) vs. CD4+ T cell count for each of the analytes showing a significant correlation between the two parameters. A linear regression line is included on each plot. P values and r² values are shown in Table 3a and b.

Figure 2. Cytokine correlation with HIV plasma viral load and CD4+ T cell count

(a) Plots show log(cytokine level) vs. log(viral load) or (b) log(cytokine level) vs. CD4+ T cell count for each of the analytes showing a significant correlation between the two parameters. A linear regression line is included on each plot. P values and r² values are shown in Table 3a and b.