Jose R Castillo-Mancilla1, Mary Morrow2, Yap Boum3, Helen Byakwaga4,5, Jessica E Haberer6, Jeffrey N Martin5, David Bangsberg7, Samantha Mawhinney2, Nicholas Musinguzi4, Yong Huang5, Russell P Tracy8, Tricia H Burdo9, Kenneth Williams10, Conrad Muzzora4, Peter W Hunt5, Mark J Siedner4,6. 1. Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO. 2. Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO. 3. Epicentre, MSF, Mbarara, Uganda. 4. Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda. 5. Department of Medicine, University of California San Francisco, San Francisco, CA. 6. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 7. School of Public Health, Oregon Health and Science University-Portland State University, Portland, OR. 8. Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT. 9. Department of Neuroscience, Temple University, Philadelphia, PA. 10. Biology Department, Boston College, Chestnut Hill, MA.
Abstract
BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, and the kynurenine/tryptophan ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naive adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit. Adherence was measured through medication event monitoring system and calculated as the ratio of observed/prescribed device openings per participant. We fit adjusted linear regression models to estimate the association between ART adherence and the log-transformed plasma concentrations of inflammatory biomarkers. RESULTS: We evaluated 282 participants (median age, 35 years; 70% women). The median (interquartile range) adherence was 93% (84-98). In the adjusted analyses, for every 10% increase in average ART adherence, we found a 15% [P < 0.0001; 95% confidence interval (CI), -21.0 to -7.9], 11% (P = 0.017; 95% CI, -18.3 to -2.0), and 3% (P = 0.028; 95% CI, -5.0 to -0.3) decrease in IL-6, D-dimer, and sCD14, respectively. CONCLUSIONS: Higher ART adherence was associated with lower levels of biomarkers of inflammation, immune activation, and coagulopathy among Ugandans living with HIV who achieved viral suppression shortly after ART initiation. This suggests that ART adherence could have biological consequences beyond viral suppression. Whether ART adherence optimization in virologically suppressed individuals could reduce residual inflammation remains unknown.
BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, and the kynurenine/tryptophan ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naive adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit. Adherence was measured through medication event monitoring system and calculated as the ratio of observed/prescribed device openings per participant. We fit adjusted linear regression models to estimate the association between ART adherence and the log-transformed plasma concentrations of inflammatory biomarkers. RESULTS: We evaluated 282 participants (median age, 35 years; 70% women). The median (interquartile range) adherence was 93% (84-98). In the adjusted analyses, for every 10% increase in average ART adherence, we found a 15% [P < 0.0001; 95% confidence interval (CI), -21.0 to -7.9], 11% (P = 0.017; 95% CI, -18.3 to -2.0), and 3% (P = 0.028; 95% CI, -5.0 to -0.3) decrease in IL-6, D-dimer, and sCD14, respectively. CONCLUSIONS: Higher ART adherence was associated with lower levels of biomarkers of inflammation, immune activation, and coagulopathy among Ugandans living with HIV who achieved viral suppression shortly after ART initiation. This suggests that ART adherence could have biological consequences beyond viral suppression. Whether ART adherence optimization in virologically suppressed individuals could reduce residual inflammation remains unknown.
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