Are serotonin alterations the link between thrombocytopenia and poor immune status among HIV infected individuals?

María José Míguez-Burbano, Allan E Rodriguez, Mayra Vargas, Gabriella Tantalean, Ranjini Valiathan, Wenyaw Chan

Research output: Contribution to journalArticle

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Abstract

Objective: Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. Methods: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). Results: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. Conclusions: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications.

Original languageEnglish
Article number1000277
JournalJournal of AIDS and Clinical Research
Volume5
Issue number2
DOIs
StatePublished - Jan 1 2014

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Idiopathic Thrombocytopenic Purpura
Brain-Derived Neurotrophic Factor
Serotonin
Alcohols
HIV
Thrombocytopenia
Multivariate Analysis
Serotonin Plasma Membrane Transport Proteins
Highly Active Antiretroviral Therapy
Serotonin Uptake Inhibitors
CD4 Lymphocyte Count
Blood Platelets
Lymphocytes
Therapeutics
Population

Keywords

  • Alcohol
  • BDNF
  • HIV/ AIDS
  • Serotonin
  • Thrombocytopenia

ASJC Scopus subject areas

  • Infectious Diseases
  • Dermatology
  • Immunology
  • Virology

Cite this

Are serotonin alterations the link between thrombocytopenia and poor immune status among HIV infected individuals? / Míguez-Burbano, María José; Rodriguez, Allan E; Vargas, Mayra; Tantalean, Gabriella; Valiathan, Ranjini; Chan, Wenyaw.

In: Journal of AIDS and Clinical Research, Vol. 5, No. 2, 1000277, 01.01.2014.

Research output: Contribution to journalArticle

Míguez-Burbano, María José ; Rodriguez, Allan E ; Vargas, Mayra ; Tantalean, Gabriella ; Valiathan, Ranjini ; Chan, Wenyaw. / Are serotonin alterations the link between thrombocytopenia and poor immune status among HIV infected individuals?. In: Journal of AIDS and Clinical Research. 2014 ; Vol. 5, No. 2.
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abstract = "Objective: Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. Methods: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). Results: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14{\%}. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25{\%} versus HAU: 15{\%} versusnon-HAU: 10{\%}). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. Conclusions: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications.",
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AU - Míguez-Burbano, María José

AU - Rodriguez, Allan E

AU - Vargas, Mayra

AU - Tantalean, Gabriella

AU - Valiathan, Ranjini

AU - Chan, Wenyaw

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N2 - Objective: Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. Methods: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). Results: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. Conclusions: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications.

AB - Objective: Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. Methods: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). Results: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. Conclusions: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications.

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