Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.
OBJECTIVE
To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection.


METHODS
Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition.


RESULTS
The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status.


CONCLUSIONS
These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.
Benton
Tami
T
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Lynch
Kevin
K
Dubé
Benoit
B
Gettes
David R
DR
Tustin
Nancy B
NB
Ping Lai
Jian
J
Metzger
David S
DS
Blume
Joshua
J
Douglas
Steven D
SD
Evans
Dwight L
DL
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000635:transmission / Q000821:virology*; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D012701:Serotonin / Q000276:immunology / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors