One of the many issues that HIV health care providers should consider to improve outcomes for patients is identifying methamphetamine use and how to help patients reduce or stop their use, according to presenters at one panel during IDWeek 2024 in Los Angeles.
Jennifer Fulcher, MD, an associate professor at the David Geffen School of Medicine at UCLA, explored the epidemiology of stimulant use among people living with HIV (PLWH) and explained how stimulants, especially methamphetamine, exacerbate inflammation in HIV and why the risk of acquiring HIV among people who use meth goes beyond the behavioral effects of the drug.
The impact of meth
The strong correlation between meth use and new HIV cases isn’t the only cause for concern, Fulcher said. Methamphetamine use leads to worse HIV-related outcomes.
“There’s less engagement in care, there’s less ART [antiretroviral treatment] adherence, increased ART resistance, disease progression, CD4 decline and increase in HIV-associated neurocognitive disorders [for PLWH who use meth],” she said. “And what has been reported in many studies is decreased viral suppression, and at least two different studies have found that [decreased viral suppression] still occurs even when somebody is taking ART.”
In anyone, meth use increases the chances of developing mental health disorders, neurocognitive disorders, oral health problems and cardiovascular risk, including increased pulmonary hypertension. For PLWH, meth use brings a host of other complications, including increased HIV transmission and replication in certain cells, and increased systemic inflammation and immune activation, which causes a feedback loop of inflammation-related HIV replication. Fulcher pointed to a 2018 study that showed an increase in rectal inflammatory cytokines [small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells] following recent meth use, which was true regardless of HIV serostatus, age, sex and receptive anal intercourse.
“So, by way of increasing this mucosal inflammation, inducing barrier damage and attracting and activating target cells, that makes it a much more risky area and risky time for HIV transmission,” she said.
Also adversely affecting the long-term health of PLWH is the drug’s effect on the gut microbiome (which can affect users regardless of their HIV status). But because meth use in PLWH contributes to ongoing gut inflammation, Fulcher said, it can contribute to chronic immune activation and systemic inflammation that contributes to many HIV-related comorbidities.
Methamphetamine can decrease blood-brain barrier function, which can increase neuro inflammation that then feeds into immune cell activation, viral replication and progression of neuroAIDS (any neurologic condition stemming from HIV) and HIV-associated neurocognitive disorders, she said.
These negative outcomes occur even when a person living with HIV is taking ART and attending their appointments. “The drug is to blame here,” she said. “It’s not just the behavior.”
Nearly 10 million people in the United States used stimulants in the past year, estimates the National Survey on Drug Use and Health. Fulcher noted that substance use in general is more prevalent among sexual minority populations, both men and women, and highly prevalent among men who have sex with men and in PLWH. “The estimated stimulant use among people living with HIV is between five and 15%, which is markedly higher than the general population,” she said. Drawing an association between methamphetamine and HIV acquisition, Fulcher pointed to the results of an online cohort study of about 5,000 sexual and general minority persons which found that methamphetamine use accounted for up to one-third of new HIV diagnoses.
Is there a role for HIV clinicians?
Fulcher said HIV clinics can take an active role in weaning patients off methamphetamines, but must do so with care, in a non-stigmatizing and non-judgmental way, with an understanding of the context of stimulant use.
Any substance use treatment, even if it’s not specifically for stimulant use, could be helpful, Fulcher said. In Los Angeles-based cohort research, the Mstudy, which looked at methamphetamine use trajectories, researchers found that people who received any type of substance use treatment—for tobacco, alcohol, opioids or any combination of the above—reduced their methamphetamine use by almost half. “Engaging people in any kind of treatment or recovery could be beneficial,” she said.
Even switching the type of ART could help harm reduction. A 2023 demonstration project from Zuckerberg San Francisco General Hospital’s Ward 86 HIV clinic, where about a third of the population actively used stimulants, found that switching to long-acting ART significantly improved viral suppression, though it didn’t conclude why.
Fulcher said that abstinence from different drugs provides better viral suppression; especially with methamphetamine, even a reduction in the frequency of use can have a significant effect on viral suppression, as well as other health outcomes. “Encouraging patients to reduce the frequency of their use can have a lot of benefit,” Fulcher said.
Treatment options for methamphetamine use
Fulcher discussed several options for health care workers to treat people who use meth, including contingency management and medication.
Contingency management is a behavioral intervention with motivational incentives, such as gift cards, often with escalating value for positive behavior that would reward evidence such as a negative urine drug screen for meth users. Multiple randomized clinical trials, she said, support the efficacy of contingency management, either alone or in combination with other strategies.
Contingency management does have challenges, she noted. “It takes additional time and staffing, because you need the patients to come back, either weekly or every other week. And especially if [a clinic is] using federal funds, there’s financial limitations on how much a patient could receive as a reward, so that can really hinder your ability to provide a truly motivational reward.”
Still, if implemented well, contingency management can improve HIV-related outcomes. A pilot study from the University of California at San Francisco combined contingency management for substance use disorder and treatment of infectious complications. The study, conducted in an acute care setting, used a “fishbowl strategy”—every time patients met a goal, they were allowed to reach into a fishbowl to draw a prize.
“[Patients] had an incredibly high rate of antibiotic completion, a high rate of abstinence from drug use,” Fulcher said. “You can imagine how a strategy like this could be used also in the HIV clinic to incentivize attending appointments and ART adherence.”
Two medications, naltrexone, in combination with bupropion, as well as mirtazapine, could be used to manage substance use.
“Bupropion can be beneficial for people who enjoy the weak stimulant effect,” Fulcher said. “It also is FDA approved for smoking cessation, so if you have a patient who also uses tobacco, this could be a great option. Naltrexone is FDA approved for alcohol and opioid use disorder, so it can be used to co-manage those, though it can increase risk of opioid overdose. Mirtazapine, an FDA approved antidepressant, can be beneficial in patients with mood disorder, but has side effects of weight gain and sleepiness.”
A 2021 study published in the New England Journal of Medicine found that for people with moderate to severe meth use disorder, treatment with a combination of extended-release naltrexone plus daily oral extended-release bupropion over a 12-week period “resulted in a higher response than a placebo.”
Two randomized clinical trials, both in men who have sex with men, found that mirtazapine resulted in a decrease in methamphetamine use as secondary outcomes. “[Researchers] also looked at sexual risk behaviors, which they defined by varying measures, and found a decrease in that as well as no adverse effects,” Fulcher said.
Treating the whole person in a substance use clinic
In the same session, Hermione Hurley, MD, an associate professor at the University of Colorado, made a case for a “concurrent context of care” for PLWH who use stimulants and other substances. Providing examples from the Denver Center for Addiction Medicine, a public health use disorder (PHUD) clinic, Hurley said the mission is to provide low barrier to access and counseling, while improving engagement for HIV care. “There is a lot of stimulant use disorder in Colorado,” she said, and that patients do not need to be sober to seek HIV care at the clinic.
Hurley began with a plea to attendees: never withhold HIV meds for people actively using substances. “Please give people the medicines,” she said. “It both invests in them in the long-term, and they will be successful,” she said. “This is really a ‘no wrong door’ model.”
Decreasing stigma with person-first language and care is crucial to serve this population, she added. “We made a de-stigmatizing name, PHUD, and that means you can check in at the front desk and know that you’re not going to be judged in the hallway,” she said. “You’re just coming to the other ID [infectious disease] clinic and all the other things that people would normally do for HIV. It doesn’t identify you clearly as someone who has a concurrent substance use disorder.” But they will have access to clinic support staff, patient access specialists, ID social work, behavioral health and ID medication management.”
“We co-locate with other kind of really high-value colleagues and clinics that we use as part of our Ryan White funding,” she said.
Hurley’s second suggestion for substance use clinics that aim to treat the whole patient: standardize intake labs for hep A, B, C and HIV. “One draw and you’re done. You’ve really got to grovel to your lab directors. But boy, this makes a huge difference,” she said.
“In a large urban setting where I have syringe service programs, I am finding a lot of hepatitis C [and finding] hepatitis B cases among people injecting methamphetamine who are older than sort of 35 to 60, too old to have received childhood vaccinations.”
Hurley also recommended that ID generalists or specialists with the inclination should help out in a rural community. “Rural areas [are] where I’m seeing more new diagnoses associated with substance use, because it is hard for people to drive to a syringe service program.”
And wherever they practice, professionals should consider the patient’s butt, Hurley said, noting the high risk of anal cancer for PLWH. “Some of the people that will always stay with me actually had terrible anal cancers, and they never felt that they could tell me after almost a decade.”