Cocaine Could Make You Susceptible to HIV, Says UCLA

New UCLA research offers further evidence that cocaine use disrupts the immune system, making one more likely to become infected with HIV.

In research published online June 18 in the peer reviewed journal Scientific Reports, researchers with the UCLA AIDS Institute and Center for AIDS Research used an advanced form of humanized mice -- that is, immunodeficient mice that have a human-like immune system -- to study the effects of cocaine. The findings suggest that the narcotic makes one significantly more susceptible to HIV infection than people who don't use the drug.

"Substance use and abuse is a major issue, especially when it comes to HIV infection, said Dimitrios Vatakis, assistant professor of medicine in the division of hematology/oncology at the David Geffen School of Medicine at UCLA, and the study's senior author. "There has been a general attitude, especially in the scientific but also the general community, that risky behavior is the main reason for higher infections. This study shows that under the same transmission conditions, drug exposure enhances infection through a collective of biological changes."

This study builds on previous research by Vatakis and others on his team finding that a three-day exposure to cocaine appears to make the cells more susceptible to HIV infection by stimulating two receptors in the cells, called D1 and D4. Those findings suggested that cocaine use increases the pool of T cells in the human body that can become infected by the virus. As a result, the odds for both significant infection and new production of the virus increased.

That study, however, was based on in-vitro research, which could have skewed the results. The next step was to find the same effect in in-vivo studies. This is what the current paper has done.

For this study, Vatakis and team used the most advanced humanized mouse model, called BLT. These mice are transplanted with human hematopoietic stem cells and donor matched thymus and liver tissues, resulting in the development of a functioning human immune system.

"This study is the first of its kind using this model," said Vatakis, who also directs the UCLA/CFAR Virology Core Laboratory. "The BLT has been used to study HIV latency, cancer immunotherapy and now drug abuse and HIV infection. It very closely resembles the human condition and it is the most relevant."

The researchers separated the mice into two major groups: one that would be injected with saline and another receiving 5 mg/kg of cocaine per day. Each group was treated with these combinations for five days.

After five days half the mice in each group were injected intraperitoneally with HIV-1. All groups, infected and non-infected, continued to be given saline or cocaine for two more weeks. The researchers then collected blood and tissue samples to measure infection levels and examine other cocaine mediated effects. They found that the cocaine/HIV group had higher viral loads than the saline/HIV mice. They also found that a higher proportion of the saline/HIV mice (nine of 19) had undetectable viral loads, compared with only three of the 19 cocaine/HIV mice.

The researchers were surprised to find that despite the cocaine induced inflammation prior to infection, the CD4 T cells that HIV targets were not very activated. Also, the CD8 T cells that the immune system uses to clear infected cells were not functional, even though they appeared to be active.

"This points to cocaine blunting the potency of our body's defense against the virus," Vatakis said.

While these studies have shed further light on the effects of cocaine use and misuse on HIV infection, this small animal model, even though closely mimicking human immunity, does not fully recreate real life settings. In addition, the study used an acute -- or brief -- cocaine exposure regimen, rather than a more clinically relevant chronic use model. Thus, within this context, some of the observed patterns may be more biased.

The next stage of research, using the same BLT model, will be to determine how cocaine abuse might affect HIV transmission in mucosal membranes such as vaginal and anal tissues; how pre- and post-exposure prophylaxis can affect cocaine exposure; how cocaine might accelerate viral latency, the process in which a virus lies dormant in a cell; and how cocaine alters the body's immune defenses and affects other viral infections.

Co-authors are Sohn G. Kim, Emily L. Lowe, Dhaval Dixit, Cindy Seyeon Youn, Irene J. Kim, James B. Jung, Robert Rovner Jr., and Jerome A. Zack of UCLA.

National Institutes of Health grants R21DA031036-01A1, 5P30 AI028697 and R01AI070010 funded this study.