EXPERT ANALYSIS FROM WPA 2017
BERLIN (FRONTLINE MEDICAL NEWS) – From cellular pathology to socioeconomics, methamphetamine and HIV are a devastating combination.
Either one is enough to ruin a life on its own. But together they can become a fatal ouroboros, Jordi Blanch, MD , said at the meeting of the World Psychiatric Congress. The drug sparks dangerous sexual behavior that ups HIV risk. It increases HIV-vulnerable receptors on immune cells, priming them for viral invasion. It interferes with the metabolism of antiretroviral drugs and grinds medication adherence into the dust.
And even when faced with the facts about these interactions with a serious disease, meth users find it almost impossible to leave the drug behind.
Methamphetamine was once almost exclusively a North American problem, said Dr. Blanch of the University of Barcelona. But in the last decade, the drug has jumped the pond, storming the beaches of Western Europe. Bolstered by imports from Asia, it’s now spreading eastward and down into Africa. Meth is challenging and surpassing alcohol as the drug of choice for HIV high-risk groups (particularly men who have sex with men). Like alcohol, it’s cheap and easy to find. Unlike alcohol, it delivers an incredibly potent, nearly instantaneous brain hit that amps up sexual desire and capacity while decreasing inhibition and executive function.
“When we look at the use of meth in the context of sexual relationships, it’s not hard to understand how it leads to all kinds of sexually transmitted infections, including HIV,” Dr. Blanch said. “And since meth has made its way to Western Europe, we are seeing a big increase in meth-related HIV cases.”
A potent dopamine agonist, meth not only increases the neurotransmitter’s release, it blocks reuptake. It reduces the expression of dopamine transporters on the cell surface. At the same time, meth inhibits monoamine oxidase, normally a prime metabolizer. It even creates more dopamine: Methamphetamine increases the activity of tyrosine hydroxylase, the enzyme that catalyzes tyrosine into the dopamine precursor, l-dopa.
The neurologic response to smoking crystal meth – still the most popular way of ingesting the drug – is practically instantaneous. “It’s a very fast and intense euphoric high that, as we know, can have a lot of really bad side effects, like anxiety, restlessness, and even psychosis,” Dr. Blanch said. Its other side effects, though, are what make meth such a potent driver of risky sexual behavior.
“Men who have sex with men use it because it dramatically facilitates sexual functioning. It allows them to have sex for much longer. It decreases pain sensation, so this makes it easier to engage in anal sex, which is likely to be unprotected,” Dr. Blanch said. At the same time, the drug decreases higher-order thinking and increases impulsivity, driving even more behaviors that increase the risk of HIV, including group sex and the use of alcohol and injectable drugs together.
It is not just a cognitive-behavioral problem, though. Animal studies have found some intriguing pathophysiologic links between HIV viral activity and meth.
“Meth actually facilitates the infection,” Dr. Blanch said. “The risk of getting it is much higher, and the risk of it progressing with a high viral load is much higher.”
A 2015 review paper by Ryan Colby Passaro and his associates touches on some of these animal models ( J Neuroimmune Pharmacol. 2015 Sep;10[3]:477-86 ). One of the most intriguing is a mouse study, which found that methamphetamine upregulated the HIV-1 coreceptors, CXCR4 and CCR5, not only on CD4+ T cells, but on monocytes, macrophages, dendritic cells, and, to some extent, astrocytes.
Cat and rhesus monkey data implicated this meth-related effect on CXCR4 and CCR5 as well. But the drug also was implicated in other cellular pathways – all of which serve to make immune cells more vulnerable to HIV attack. These findings support the observation that methamphetamine users with the disease frequently have higher viral loads than nonusers.
After a diagnosis, users may continue to use as a way of avoiding confronting their illness, or even to combat the accompanying physical fatigue, Dr. Blanch said. Like many illicit drug users, meth users often show poor compliance with medical follow-up and poor medication adherence. But even if they do take their antiretroviral medications, methamphetamine still has a way of exerting its power. Ritonavir and cobicistat both inhibit the metabolic pathway that breaks down methamphetamine; using meth with either of those drugs can increase meth concentrations by up to 10-fold, a combination that has killed many patients.
Unfortunately, Dr. Blanch said, it’s terribly difficult for users to give up meth, even in the face of contracting such a serious illness.
“In the beginning, after a diagnosis, they may stop using for a while. But then many start again,” he said. “We see this in study after study. But we have not so many studies on how to treat these patients.”
Trials of antidepressants and antipsychotics, and of replacement therapy with amphetamines or methylphenidate, have had mixed results.
“In my own clinic, we try to explain these problems of the interaction of meth and HIV. We have tried even to motivate our patients to use just on the weekend, for example, but they didn’t accept that,” he said. “Usually, we end up trying to make an agreement that the patient will use as little as possible and let them know how much it interferes with their treatment. But in my clinical experience, it’s not so easy. It’s hard to make any change. … very difficult.”
Dr. Blanch had no relevant financial disclosures.
On Twitter @alz_gal
