Partial Normalization of Biomarkers of Inflammation and Immune Activation Among Virally Suppressed Men With HIV Infection and High ART Adherence

Abstract

Background: The objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men.

Methods: We analyzed person-visits with available biomarker data from the Multicenter AIDS Cohort Study (MACS) among MWH receiving ART with HIV RNA <50 copies/mL and among HIV-uninfected men. Self-reported adherence was classified as 100% if no missed ART doses in the past 4 days were reported. We evaluated associations between ART adherence and concentrations of 24 serum biomarkers compared with HIV-uninfected visits using a generalized gamma model, adjusting for potential confounders.

Results: Person-visits (2565 from MWH reporting 100% ART adherence and 1588 from HIV-uninfected men) from a total of 1469 men were included in the analysis. Serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), IL-1β, interferon-γ (IFN-γ), chemokine C-C motif ligand 2 (CCL2), and CCL14 from person-visits among MWH who reported 100% adherence were similar to HIV-uninfected person-visits. Comparatively higher concentrations of 11 biomarkers and lower concentrations of 7 biomarkers were observed in person-visits from MWH who reported 100% ART adherence, compared with HIV-uninfected person-visits.

Conclusions: Although MWH with virologic suppression who reported 100% ART adherence exhibited overall higher concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men, some biomarker concentrations were similar in both groups. These findings suggest that optimal ART adherence could have clinical implications beyond achieving and sustaining viral suppression.

Keywords: HIV; adherence; antiretroviral therapy; inflammation.

Figure 1.

Percent shifts in distribution of biomarker concentrations in person-visits from MWH with 100% and <100% 4-day self-reported ART adherence, compared with HIV-uninfected person-visits. Biomarker data were analyzed at person-visits where HIV-infected men reported taking ART and had plasma HIV RNA levels <50 copies/mL. Person-visits were considered adherent (squares) if self-reported adherence for the previous 4 days was 100%, and nonadherent (circles) if reported adherence for the previous 4 days was <100%. Generalized gamma models were adjusted for age, race, hepatitis B and C virus infection, smoking, depressive symptoms, diabetes mellitus, anemia, hypertension, and CD4+ T-lymphocyte cell count. Error bars represent 95% confidence intervals. Red-filled squares and blue-filled circles indicate hazard ratios that are statistically significant at P < .05. Abbreviations: ART, antiretroviral therapy; BAFF, B-cell activating factor; CCL, chemokine C-C motif ligand; CRP, C-reactive protein; CXCL, chemokine C-X-C motif ligand; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-γ, interferon γ; IL, interleukin; MWH, men with HIV; sCD14, soluble CD14; sCD27, soluble CD27; sgp130, soluble glycoprotein 130; sIL-2Rα, soluble IL-2 receptor-α; sIL-6R, soluble IL-6 receptor; sTNF-R2, soluble tumor necrosis factor receptor 2; TNF-α, tumor necrosis factor α.