Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression

Nicholas Musinguzi, Jose Castillo-Mancilla, Mary Morrow, Helen Byakwaga, Samantha Mawhinney, Tricia H. Burdo, Yap Boum, Conrad Muzoora, Bosco M. Bwana, Mark J. Siedner, Jeffrey N. Martin, Peter W. Hunt, David R. Bangsberg, Jessica E. Haberer

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. SETTING: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8 T-cell activation (HLA-DR/CD38 coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. RESULTS: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR/CD8 (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. CONCLUSIONS: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.

Original languageEnglish (US)
Pages (from-to)386-391
Number of pages6
JournalJournal of acquired immune deficiency syndromes (1999)
Volume82
Issue number4
DOIs
StatePublished - Dec 1 2019

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Inflammation
HLA-DR Antigens
Interleukin-6
Kynurenine
Uganda
Therapeutics
Viral Load
Tryptophan
Linear Models
Referral and Consultation
Biomarkers
HIV
T-Lymphocytes
fibrin fragment D
thymidine 5'-phosphonate

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression. / Musinguzi, Nicholas; Castillo-Mancilla, Jose; Morrow, Mary; Byakwaga, Helen; Mawhinney, Samantha; Burdo, Tricia H.; Boum, Yap; Muzoora, Conrad; Bwana, Bosco M.; Siedner, Mark J.; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.; Haberer, Jessica E.

In: Journal of acquired immune deficiency syndromes (1999), Vol. 82, No. 4, 01.12.2019, p. 386-391.

Research output: Contribution to journalArticle

Musinguzi, N, Castillo-Mancilla, J, Morrow, M, Byakwaga, H, Mawhinney, S, Burdo, TH, Boum, Y, Muzoora, C, Bwana, BM, Siedner, MJ, Martin, JN, Hunt, PW, Bangsberg, DR & Haberer, JE 2019, 'Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression', Journal of acquired immune deficiency syndromes (1999), vol. 82, no. 4, pp. 386-391. https://doi.org/10.1097/QAI.0000000000002148
Musinguzi, Nicholas ; Castillo-Mancilla, Jose ; Morrow, Mary ; Byakwaga, Helen ; Mawhinney, Samantha ; Burdo, Tricia H. ; Boum, Yap ; Muzoora, Conrad ; Bwana, Bosco M. ; Siedner, Mark J. ; Martin, Jeffrey N. ; Hunt, Peter W. ; Bangsberg, David R. ; Haberer, Jessica E. / Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression. In: Journal of acquired immune deficiency syndromes (1999). 2019 ; Vol. 82, No. 4. pp. 386-391.
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AU - Musinguzi, Nicholas

AU - Castillo-Mancilla, Jose

AU - Morrow, Mary

AU - Byakwaga, Helen

AU - Mawhinney, Samantha

AU - Burdo, Tricia H.

AU - Boum, Yap

AU - Muzoora, Conrad

AU - Bwana, Bosco M.

AU - Siedner, Mark J.

AU - Martin, Jeffrey N.

AU - Hunt, Peter W.

AU - Bangsberg, David R.

AU - Haberer, Jessica E.

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N2 - BACKGROUND: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. SETTING: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8 T-cell activation (HLA-DR/CD38 coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. RESULTS: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR/CD8 (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. CONCLUSIONS: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.

AB - BACKGROUND: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. SETTING: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8 T-cell activation (HLA-DR/CD38 coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. RESULTS: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR/CD8 (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. CONCLUSIONS: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.

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