Brief Report

Higher ART Adherence Is Associated with Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression

Jose R. Castillo-Mancilla, Mary Morrow, Yap Boum, Helen Byakwaga, Jessica E. Haberer, Jeffrey N. Martin, David Bangsberg, Samantha Mawhinney, Nicholas Musinguzi, Yong Huang, Russell P. Tracy, Tricia H. Burdo, Kenneth Williams, Conrad Muzzora, Peter W. Hunt, Mark J. Siedner

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume77
Issue number5
DOIs
StatePublished - Apr 15 2018

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Inflammation
Therapeutics
HIV
Confidence Intervals
Linear Models
Interleukin-6
Biomarkers
Kynurenine
Nevirapine
Tryptophan
Thymidine
RNA
T-Lymphocytes
Equipment and Supplies

Keywords

  • adherence
  • antiretroviral therapy
  • inflammation
  • Uganda

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Brief Report : Higher ART Adherence Is Associated with Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression. / Castillo-Mancilla, Jose R.; Morrow, Mary; Boum, Yap; Byakwaga, Helen; Haberer, Jessica E.; Martin, Jeffrey N.; Bangsberg, David; Mawhinney, Samantha; Musinguzi, Nicholas; Huang, Yong; Tracy, Russell P.; Burdo, Tricia H.; Williams, Kenneth; Muzzora, Conrad; Hunt, Peter W.; Siedner, Mark J.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 77, No. 5, 15.04.2018, p. 507-513.

Research output: Contribution to journalArticle

Castillo-Mancilla, JR, Morrow, M, Boum, Y, Byakwaga, H, Haberer, JE, Martin, JN, Bangsberg, D, Mawhinney, S, Musinguzi, N, Huang, Y, Tracy, RP, Burdo, TH, Williams, K, Muzzora, C, Hunt, PW & Siedner, MJ 2018, 'Brief Report: Higher ART Adherence Is Associated with Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression', Journal of Acquired Immune Deficiency Syndromes, vol. 77, no. 5, pp. 507-513. https://doi.org/10.1097/QAI.0000000000001629
Castillo-Mancilla, Jose R. ; Morrow, Mary ; Boum, Yap ; Byakwaga, Helen ; Haberer, Jessica E. ; Martin, Jeffrey N. ; Bangsberg, David ; Mawhinney, Samantha ; Musinguzi, Nicholas ; Huang, Yong ; Tracy, Russell P. ; Burdo, Tricia H. ; Williams, Kenneth ; Muzzora, Conrad ; Hunt, Peter W. ; Siedner, Mark J. / Brief Report : Higher ART Adherence Is Associated with Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression. In: Journal of Acquired Immune Deficiency Syndromes. 2018 ; Vol. 77, No. 5. pp. 507-513.
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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.",
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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.

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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.

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