Persistent immune ac activation an and depression am among Ugan - - PowerPoint PPT Presentation

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Persistent immune ac activation an and depression am among Ugan - - PowerPoint PPT Presentation

May 29, 2023 323 likes •478 views

Persistent immune ac activation an and depression am among Ugan andan ans in init itia iatin ing ART Jonathan L. Chang, Nicholas Musinguzi, Alexander C. Tsai, Conrad Muzoora, Mwebesa Bwana, Yap Boum, Russell Tracy, Jeff N. Martin,

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Persistent immune ac activation an and depression am among Ugan andan ans in init itia iatin ing ART

Jonathan L. Chang, Nicholas Musinguzi, Alexander C. Tsai, Conrad Muzoora, Mwebesa Bwana, Yap Boum, Russell Tracy, Jeff N. Martin, Jessica E. Haberer, David R. Bangsberg, Peter W. Hunt, Mark J. Siedner

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SLIDE 2

Disclosures and Acknowledgement

  • No disclosures
  • I would like to acknowledge persons living with HIV in Uganda and

elsewhere for contributing generously to this research

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SLIDE 3

Bac Background und and and Metho hods ds

  • Chronic inflammation, even after effective ART, has been associated

with numerous comorbidities and mortality

  • Relationship between inflammation and depression less clear
  • 453 Ugandan adults initiating ART from 2005-2013 followed 3-4

times/year for 2 years

Byakwaga H et al., JID 2014; Siedner MJ et al., JID 2017; Lee S et al., JID 2017; Martinez P et al., JAIDS 2014

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SLIDE 4

Bac Background und and and Metho hods ds

  • Chronic inflammation, even after effective ART, has been associated

with numerous comorbidities and mortality

  • Relationship between inflammation and depression less clear
  • 453 Ugandan adults initiating ART from 2005-2013 followed 3-4

times/year for 2 years

Byakwaga H et al., JID 2014; Siedner MJ et al., JID 2017; Lee S et al., JID 2017; Martinez P et al., JAIDS 2014

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SLIDE 5

6 0.0 0.3 0.6

Month since ART start Log10 marker level Δ

Bac Background und and and Metho hods ds

  • Chronic inflammation, even after effective ART, has been associated

with numerous comorbidities and mortality

  • Relationship between inflammation and depression less clear
  • 453 Ugandan adults initiating ART from 2005-2013 followed 3-4

times/year for 2 years

Byakwaga H et al., JID 2014; Siedner MJ et al., JID 2017; Lee S et al., JID 2017; Martinez P et al., JAIDS 2014

IL-6 D-dimer sCD14 sCD163 KT ratio EXPOSURE

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SLIDE 6

6 0.0 0.3 0.6

Month since ART start Log10 marker level Δ

Bac Background und and and Metho hods ds

  • Chronic inflammation, even after effective ART, has been associated

with numerous comorbidities and mortality

  • Relationship between inflammation and depression less clear
  • 453 Ugandan adults initiating ART from 2005-2013 followed 3-4

times/year for 2 years

Byakwaga H et al., JID 2014; Siedner MJ et al., JID 2017; Lee S et al., JID 2017; Martinez P et al., JAIDS 2014

IL-6 D-dimer sCD14 sCD163 KT ratio Continuous Depressive symptom severity during first 2 years of ART use Binary probable depression EXPOSURE OUTCOME

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SLIDE 7

6 0.0 0.3 0.6

Month since ART start Log10 marker level Δ

Bac Background und and and Metho hods ds

  • Chronic inflammation, even after effective ART, has been associated

with numerous comorbidities and mortality

  • Relationship between inflammation and depression less clear
  • 453 Ugandan adults initiating ART from 2005-2013 followed 3-4

times/year for 2 years

Byakwaga H et al., JID 2014; Siedner MJ et al., JID 2017; Lee S et al., JID 2017; Martinez P et al., JAIDS 2014

IL-6 D-dimer sCD14 sCD163 KT ratio Continuous Depressive symptom severity during first 2 years of ART use

  • GEE regression models, adjusted for demographic and clinical

characteristics

Binary probable depression EXPOSURE OUTCOME

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SLIDE 8
  • 1. Depressive symptom score: continuous outcome
  • Models adjusted for age, sex, BMI, marital status, education, asset index, baseline depressive symptom score, CD4+ count, viral

load suppression, tuberculosis co-infection, time on ART, year of enrollment, heavy drinking, and smoking.

sCD14 KT ratio IL-6 D-dimer sCD163 sCD14, adjusted KT ratio, adjusted

  • 0.2
  • 0.1

0.0 0.1

6-month change in marker level (in quartiles from smallest to largest decreases) Adjusted beta (95% CI) for KT ratio for sCD14

p < 0.001 * * * * * * *

*Lowest quartile used as reference

p = 0.006 p = 0.007 p = 0.019

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SLIDE 9
  • 1. Depressive symptom score: continuous outcome
  • Models adjusted for age, sex, BMI, marital status, education, asset index, baseline depressive symptom score, CD4+ count, viral

load suppression, tuberculosis co-infection, time on ART, year of enrollment, heavy drinking, and smoking.

sCD14 KT ratio IL-6 D-dimer sCD163 sCD14, adjusted KT ratio, adjusted

  • 0.2
  • 0.1

0.0 0.1

6-month change in marker level (in quartiles from smallest to largest decreases) Adjusted beta (95% CI) for KT ratio for sCD14

p < 0.001 * * * * * * *

*Lowest quartile used as reference

p = 0.006 p = 0.007 p = 0.019

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SLIDE 10
  • 1. Depressive symptom score: continuous outcome
  • Models adjusted for age, sex, BMI, marital status, education, asset index, baseline depressive symptom score, CD4+ count, viral

load suppression, tuberculosis co-infection, time on ART, year of enrollment, heavy drinking, and smoking.

  • 2. Probable depression:

binary outcome

sCD14 KT ratio IL-6 D-dimer sCD163 sCD14, adjusted KT ratio, adjusted

  • 0.2
  • 0.1

0.0 0.1

6-month change in marker level (in quartiles from smallest to largest decreases) Adjusted beta (95% CI) for KT ratio for sCD14

p < 0.001 * * * * * * *

*Lowest quartile used as reference

p = 0.006 p = 0.007 p = 0.019

slide-11
SLIDE 11
  • 1. Depressive symptom score: continuous outcome
  • Models adjusted for age, sex, BMI, marital status, education, asset index, baseline depressive symptom score, CD4+ count, viral

load suppression, tuberculosis co-infection, time on ART, year of enrollment, heavy drinking, and smoking.

  • 2. Probable depression:

binary outcome

sCD14 KT ratio IL-6 D-dimer sCD163 sCD14, adjusted KT ratio, adjusted

  • 0.2
  • 0.1

0.0 0.1

6-month change in marker level (in quartiles from smallest to largest decreases) Adjusted beta (95% CI) for KT ratio for sCD14

p < 0.001 * * * * * * *

*Lowest quartile used as reference

p = 0.006 p = 0.007 p = 0.019

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SLIDE 12

Di Discus ussion

  • Greater decreases in inflammatory biomarkers, particularly sCD14

and KT ratio, were associated with lower future depressive symptoms after ART initiation

  • Additional measures, beyond suppressive ART, may be necessary to

reduce mental health disturbances in persons living with HIV

  • Measures that target macrophage activation and tryptophan

metabolism may be effective

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SLIDE 13

Re References

  • 1. Byakwaga H, Boum Y, Huang Y, et al. The kynurenine pathway of tryptophan catabolism,

CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral

  • therapy. J Infect Dis. 2014;210(3):383-391.
  • 2. Lee S, Byakwaga H, Boum Y, et al. Immunologic pathways that predict mortality in HIV-

infected Ugandans initiating antiretroviral therapy. J Infect Dis. 2017;215(8):1270-1274.

  • 3. Siedner MJ, Kim JH, Nakku RS, et al. Persistent immune activation and carotid

atherosclerosis in HIV-infected Ugandans receiving antiretroviral therapy. J Infect Dis. 2016;213(3):370-378.

  • 4. Martinez P, Tsai AC, Muzoora C, et al. Reversal of the Kynurenine pathway of tryptophan

catabolism may improve depression in ART-treated HIV-infected Ugandans. J Acquir Immune Defic Syndr. 2014;65(4):456-462.