Fueling the Fire

“It’s the government’s way of controlling people,” remarked one patient with HIV when asked about his interest in restarting antiretroviral medications. He was at the Dallas County Hospital for evaluation of unintentional weight loss, and his paranoia was thought to be a consequence of methamphetamine (meth) use, a habit that he wanted to break but continued to struggle with. “I don’t know how to change it.” Unfortunately, his story is one of many that hints at the complex relationship between HIV and meth.

History of the HIV and Methamphetamine Syndemic in the United States

The HIV and meth epidemics of the United States (U.S.) began in the late 20th century and continue to this day. In 1970, the U.S. government rescheduled amphetamine-type stimulants (ATS) to a more restricted drug class, thereby limiting access to the public.¹ In response, some citizens started producing and distributing meth countrywide.^1,2 Consumption of the drug has since reached a record level, with 2.6 million domestic users in 2023.³ Similarly, in 1981, the Centers for Disease Control and Prevention published an article in the Morbidity and Mortality Weekly Report describing an outbreak of Pneumocystis pneumonia among young gay men in Los Angeles, Calif.⁴ The publication marked the dawn of AIDS in our country. Despite the ensuing discovery of HIV in 1983, advancements of antiretroviral therapy (ART) in the 1990s, and the Ending HIV Epidemic initiative in 2019, the number of people with HIV in the U.S. continues to rise, reaching 1.25 million by 2022.^5,6

By coinciding in the same geographic area and time, the HIV and meth epidemics interacted with one another in complex, synergistic ways. As a result, one might consider the individual epidemics as parts of a larger interconnected syndemic.⁷ In this article we examine the relationship between HIV and meth, using both data and insights from the experiences and perspectives of patients. We also discuss the clinical effects of meth, diagnosis of meth use disorder (MUD), and potential treatment options.

Methamphetamine Use, Morbidity, and Mortality in the United States

Although ATS are globally prevalent, with over 30 million users in 2022, meth use is more common in the U.S.^3,8 National surveillance data highlights the morbidity, mortality, and addictive potency of the drug at a country level. Among the 2.6 million Americans who reported using meth at least once in 2023, 1.8 million met the criteria for MUD.³ In other words, meth use was problematic and causing clinically-significant impairment or distress in 69 percent of users.⁹ Moreover, in 2022, meth was involved in 32 percent of 107,941 domestic deaths from overdose, second only to synthetic opioids.¹⁰ Ten years prior, meth was involved in 17 percent of 41,502 cases.¹⁰

To overdose exclusively on meth is rare.¹¹ Post-mortem analysis of 712 meth-related overdoses between 2009 and 2015 revealed that the involvement of multiple drugs was more common than the involvement of meth alone (87% vs 13%).¹¹ People who use meth may therefore believe that overdose is impossible. As one patient states, “You can’t OD on meth. I don’t care what they say.”¹² Health care providers can review warning signs of overdose, such as chest pain or excess sweating, and should caution patients that while overdose on meth is unlikely, any co-occurring drug use increases the risk of toxicity. Notably, most Americans who use meth, and most people with HIV (PWH) who use meth, use other drugs, too.^13,14 One study involving 261 methamphetamine-using men who have sex with men (MSM) who had HIV noted that 95 percent had polydrug use.¹⁴ The combined use of amphetamines and synthetic opioids is especially concerning. Some individuals use the two drugs to “balance” their effects or achieve a “specific type of high,” without recognizing the risk of mixed toxicity.¹⁵ Others unknowingly consume street products laced with both drugs, which can cause respiratory failure in those without opioid tolerance.¹⁶

Methamphetamine Use among Persons with HIV in the United States

Meth use is more prevalent in PWH than the general population of the U.S. MUD was reported in 13 percent of PWH from a heterogeneous cohort of 10,652 between 2007 and 2014, versus 0.6 percent of the U.S. population in 2023.^3,17 This disparity may be partially explained by the physiologic link between meth use and modes of HIV transmission. Individuals who use meth can be exposed to HIV parenterally from the sharing of injection equipment or mucosally from participation in high-risk sex.^18,19 A meta-analysis by Feelemyer et al. found that the use of ATS was associated with a two- to three-fold increased likelihood of participating in condomless sex, transactional sex, or sex with multiple partners.²⁰ Similarly, studies involving several demographic groups (MSM, heterosexual men, female sex workers) noted that meth use was associated with about a three-fold increased likelihood of HIV infection.^21-24

Beyond an immediate physiologic link, more nuanced sociodemographic and patient-related factors may underlie the relationship between HIV and meth use. Both are disproportionately prevalent in persons of the U.S. with less income, Medicaid coverage, and mental health disease.^13,25,26 Moreover, those with HIV may use stimulants to cope with the negative feelings associated with their diagnosis, such as fear of mortality, decreased self-image, or sense of disempowerment, among others.²⁷ A young PWH who was seen at the Dallas County correctional health clinic mentioned that after his diagnosis, he did not feel comfortable sharing the news with any friend or family member, and to lessen his feelings of “being alone” he turned to meth. As described by another patient, “That whole feeling numb thing is so much better than being alone.”.²⁸ PWH have also described euphoria, combating fatigue, and improving sexual experiences as primary reasons for meth use.^28,29 Overall, a number of factors seem to influence the syndemic between HIV and methamphetamines.

Clinical Effects of Methamphetamines and Diagnosis of Methamphetamine Use Disorder

Meth causes psychological and physical symptoms through complex neurochemical signals.^2,30 Time-to-peak drug effect is usually less than 20 minutes; the duration of effect is about 10 hours; and potency is dose-dependent. Certain populations favor meth over cocaine because of its pharmacodynamic qualities. Not only are methamphetamines more potent and longer-lasting than cocaine, but they are also cheaper.^29,31 After a low-to-moderate dose, individuals experience euphoria, energy, confidence and heightened sexual desires, in addition to sympathetic activation with increased heart rate, blood pressure and body temperature.^2,30,32 High doses can paradoxically cause symptoms of psychosis and, more rarely, end-organ failure.³⁰ Users have described that they “start hearing noises … [start] seeing things, awful things” or that “paranoia comes … once you take that first hit, you get paranoia.”.¹² Psychotic symptoms may last months or even years after a person has stopped using the drug.³³

Repeated use of meth can have negative health consequences across multiple organ systems, including weight loss, cognitive decline, strokes, coronary artery disease, arrhythmias, cardiomyopathy, dental decay, skin picking, and male sexual dysfunction, among others.^2,10,29,30 Importantly, repeated use of meth may also be an indicator of underlying substance use disorder (SUD), defined as two or more of the 11 criteria of problematic substance use during 12 months plus clinically-significant impairment or distress.³⁴ The criteria of problematic substance use can be organized into one of four categories (control problems, social problems, risky use, versus pharmacologic), and a greater number of positive criteria indicates a greater severity of SUD (Table 1).⁹ Health care providers should view SUD as a chronic, progressive, and relapsing disease state in patients.^2,9 By way of illustration, retrospective reviews of persons with MUD have noted relapse rates as high as 61 percent and 69 percent within one year of completing therapy.³⁵

Effects of Methamphetamine Use on HIV Outcomes

Accumulating evidence suggests that methamphetamines promote HIV disease progression, possibly through multiple mechanisms.²¹ First, meth use has been associated with decreased adherence to ART. A prospective study of 210 gay and bisexual men with HIV noted that participants were 2.3-times less likely to take ART on a given day when using meth that same day.³⁶ Additional studies have reported comparable findings.^37-39 Second, meth use has been associated with HIV viremia and decreased CD4 cell count.²¹ A retrospective review of 519 methamphetamine-using PWH and 2,573 non-users at one clinic site noted that stimulant users were more likely to have a viral load >200 copies/mL and CD4 count <200 cells/uL.⁴⁰ Moreover, among men with HIV of the Multicenter AIDS Cohort Study, meth use was noted to have a small, negative association with CD4/CD8 ratio.⁴¹ Further investigations are still needed to determine whether methamphetamines influence the molecular mechanisms of HIV replication and immune cell function, or if these respective associations are a consequence of decreased adherence to ART while using the drug.²¹ Nonetheless, the findings underscore the importance of addressing meth use in PWH to support both their general health and HIV-related outcomes.

Management of Methamphetamine Use Disorder

Three treatment options may be considered for MUD: Narcotics Anonymous (NA), psychosocial therapy, and or pharmacologic therapy.² Originating from Alcoholics Anonymous in the 1940s, NA is the oldest and largest self-help program for individuals with SUD.⁴² There are nearly 23,000 national NA groups, each composed of peers who meet frequently, maintain anonymity, and collectively strive to abstain from drugs via commitment to the Twelve Steps of Recovery.^42,43 Some people with MUD describe the social and spiritual resources of NA as valuable aids to their recovery, but the overall effectiveness of NA in reducing meth use is uncertain.^2,44 A pooled analysis of six randomized trials involving 1,730 persons with SUD noted that attendance at a 12-step program was associated with decreased substance use during the prior 30 days.⁴⁵ However, only eight percent of pooled participants reported amphetamine or methamphetamine use. As of 2023, Clinical Practice Guidelines from the American Society of Addiction Medicine (ASAM) do not offer guidance regarding the role of NA in MUD.⁴⁶

Unlike the Twelve Steps of Recovery, which are regarded to be a fixed treatment model, psychosocial therapies are personalized to the individual.⁴² A systemic review by AshaRani et al. noted that several types of psychosocial therapy (contingency management, cognitive behavioral therapy, motivational interviewing, counseling, matrix model) are effective in reducing meth use.⁴⁷ Contingency management (CM) is a unique form of therapy in which individuals are given a tangible reward for positive behavioral change, such as submitting a negative urine drug screen.⁴⁶ Systemic reviews by Brown et al. and Ronsley et al. noted that CM is not only effective for MUD but also the most effective psychosocial therapy for stimulant use disorder (StUD).^48,49 As a result, the ASAM strongly recommends the use of CM plus another psychosocial therapy for StUD, which includes but is not limited to MUD.⁴⁶ Despite its strong supporting evidence, the clinical implementation of CM has been stalled by concerns of cost, political objection, and the need to train health care staff.⁴⁹

Over 30 drugs have been assessed in randomized trials for MUD.⁵⁰ None has garnered sufficient evidence for FDA approval.⁵⁰ However, based on the results of select studies, the ASAM conditionally recommends the consideration of bupropion, bupropion plus naltrexone, topiramate, or mirtazapine as off-label treatment.⁴⁶ Each is generally well-tolerated, and has been associated with reduced meth use compared to placebo.^51-54 However, providers should note that effect sizes were small in supporting trials. For instance, in 403 persons with MUD, oral bupropion plus injectable naltrexone was associated with an increased likelihood of submitting a negative urine drug screen at weeks five through six and 11through 12 versus placebo (13.6 % vs 2.5 %).⁵² Based on these results, nine patients would need to receive therapy for one to have a positive response. The ASAM also notes that although the medications are off-label in MUD, they are FDA-approved for specific mental health diseases and SUDs that may co-occur with MUD (Table 2). In these scenarios, their use can be given extra consideration.⁴⁶ Ongoing clinical trials are evaluating ketamine, psilocybin, and tirzepatide as hopeful future treatment options (NCT06538285, NCT05322954, NCT06745128). In the meantime, health care providers considering the use of an off-label medication for MUD should engage patients in discussions about evidence, risks versus benefits, and shared decision-making.⁵⁵

Table 1: Eleven Criteria of Maladaptive Substance Use and the Severities of SUD

Table 2: Off-Label Medications for MUD