How Heroin Use Raises HIV Risk

NOVEMBER 23, 2015
Jeannette Y. Wick, RPh, MBA, FASCP
In addition to facing the risk of fatal overdose, kidney disease, and pneumonia, heroin users also have a greater likelihood of acquiring HIV.  

Morphine has been shown to increase HIV replication in a wide assortment of human cells, which include Kupffer cells, natural killer cells, T cells, B cells, polymorphonuclear leukocytes, human brain cells, and macrophages in particular.

In intravenous drug users such as heroin addicts, researchers have determined that macrophages are some of the first cells infected by HIV. Thereafter, macrophages become a viral reservoir.

In those who do not abuse drugs like heroin, interferons activate micro RNAs (miRNA) that directly bind to HIV RNA or impede intracellular processes integral to successful HIV infection. Therefore, it would be helpful to have evidence showing how heroin damages these innate protective processes.

The journal Frontiers in Microbiology recently published a study showing that heroin increases HIV infection and replication in macrophages through downregulation of HIV restriction miRNA.
The study authors collected macrophages from 14 heroin addicts and 8 control subjects.

Exclusion criteria included cardiac, renal, pulmonary, hepatic, endocrine, metabolic, or autoimmune disorders, major psychiatric disorders, and current HIV or hepatitis C status.

Direct in vitro heroin exposure to macrophages increased HIV infection and replication through a mu opioid receptor effect that could be antagonized with a receptor-specific antagonist (naltrexone).

Several specific miRNAs target the highly conserved HIV RNA 3-terminus, thereby inhibiting almost all HIV protein translation. These miRNA are particularly plentiful in CD4+ T cells and monocytes, but 4 miRNAs (miRNA-28, miRNA-125b, miRNA-150, and miRNA-382) are suppressed by in vitro heroin treatment.

Heroin’s lack of effect on miRNA-223, which is not induced by interferons, supports the hypothesis that heroin suppresses interferon alpha and beta. Heroin synergistically increases HIV replication by preserving HIV replication-required miRNA-124a/Let-7c.

In this study, heroin addicts’ macrophages had fewer HIV restriction miRNAs (miRNA-28, -125b, 150, and 382) in vivo than those from the control subjects, as well.

These findings greatly expand the understanding of how heroin increases HIV infection and replication within macrophages through downregulation of HIV restriction miRNAs.

The study authors called for further studies into other means that heroin suppresses macrophage and CD4+ cell protective mechanisms against HIV.
 


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