TY - JOUR
T1 - Brief Report
T2 - Higher ART Adherence Is Associated with Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression
AU - Castillo-Mancilla, Jose R.
AU - Morrow, Mary
AU - Boum, Yap
AU - Byakwaga, Helen
AU - Haberer, Jessica E.
AU - Martin, Jeffrey N.
AU - Bangsberg, David
AU - Mawhinney, Samantha
AU - Musinguzi, Nicholas
AU - Huang, Yong
AU - Tracy, Russell P.
AU - Burdo, Tricia H.
AU - Williams, Kenneth
AU - Muzzora, Conrad
AU - Hunt, Peter W.
AU - Siedner, Mark J.
N1 - Funding Information:
Supported by the Uganda AIDS Rural Treatment Outcomes Study is funded by US National Institutes of Health (NIH) R01 MH54907, P30 AI27763, UM1 CA181255 and the Sullivan Family Foundation. J.R.C.-M. was supported by NIH/NIAID Grants K23 AI104315 and R21 AI124859. M.J.S. was supported by the NIH (K23 MH099916) and the Harvard Center for AIDS Research (P30 AI 060354). This study was also supported by NIH Grants R56 AI100765, R21 AI078774, T32 AA007240 and P01 AI076174 and the Doris Duke Charitable Foundation (Clinical Scientist Development Award #2008047).
Publisher Copyright:
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2018/4/15
Y1 - 2018/4/15
N2 - 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.
AB - 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.
KW - Uganda
KW - adherence
KW - antiretroviral therapy
KW - inflammation
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U2 - 10.1097/QAI.0000000000001629
DO - 10.1097/QAI.0000000000001629
M3 - Article
C2 - 29346185
AN - SCOPUS:85044646115
SN - 1525-4135
VL - 77
SP - 507
EP - 513
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 5
ER -