Neurological

Fighting the Syndemic: Addressing Opioid Use Disorder and Decreasing HIV Go Hand-in- Hand

Since they began, the HIV and opioid epidemics have been inexorably entwined. In the 1980s and 1990s, HIV was common among injection drug users in inner-city minority populations. Today, the new generation of people who inject drugs tend to be young and White and reside in rural or suburban settings.1

These people, according to surveillance data,2 are faced with socioeconomic inequalities. The nonurban areas in which they live are not equipped to address the dual epidemics of opioid use and HIV. And so, in 2015, for the first time in 2 decades, the number of HIV cases directly attributed to injection drug use increased.3

There is no dearth of research into the respective HIV and opioid epidemics in the United States; for decades, investigators have been examining the hows and the whys underpinning each of these diseases. But unfortunately for researchers relying on the existing years of evidence supporting the connection between the rates of HIV infection and opioid addiction, the past few decades have drastically changed the landscape.

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The US HIV epidemic began, according to Patrick S. Sullivan, PhD, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta, Georgia, and colleagues, as a “bicoastal epidemic focused in large cities.” During the past 4 decades, however, HIV epidemiology has changed.2 Using publicly available HIV surveillance data, Dr Sullivan and colleagues were able to describe the prevalence of current and new HIV diagnoses by region, race, ethnicity, and age — data that painted a picture of a disease highly geographically concentrated in Washington, DC, Puerto Rico, and 48 other so-called hotspot counties across the country, located disproportionately in the South.2

These counties represent 52% of all new HIV diagnoses made in 2018. Of the 5 metropolitan statistical areas represented by these data, all were in southern states and Washington, DC: Orlando and Miami, Florida; Atlanta, Georgia; Baton Rouge and New Orleans, Louisiana; Baltimore, Maryland; Jackson, Mississippi; and Memphis, Tennessee.2

The researchers proposed that these geographic disparities in the rates of HIV infection are likely driven through some combination of inequitable access to treatment services, racial and ethnic composition, and the high burden of HIV infection among Black people. Although African Americans represent only 13% of the US population, they account for 41% of AIDS-related deaths.2 And although this burden is observed in both men and women, 38% of all new HIV diagnoses among men who have sex with men (MSM) were among Black individuals, and 63% of those men resided in the South.2

Rates of death from opioid overdose also have steadily increased during the past decade, doubling in the years from 2013 to 2017.1 Similar to the demographics of the HIV epidemic, the demographics of people who inject drugs also have changed. The current opioid epidemic primarily can be associated with a “new generation” of users who are White, young, and live in nonurban areas that are “poorly equipped to leverage the resources needed to address the issue,” wrote Sally L. Hodder, MD, of the West Virginia Clinical and Translational Science Institute at West Virginia University, West Virginia, and colleagues, in another study published in The Lancet.1

In addition to changing demographics, the United States has seen a steady increase in opioid-related overdose deaths since 2000, largely attributable to the use of prescription painkillers and the entrance of fentanyl into the drug supply.1 The US Centers for Disease Control and Prevention (CDC) estimates suggest that 18% of those aged 12 years and older in the United States either use illicit drugs or misuse prescription medication, which translates to upward of 70,000 drug-related deaths in 2017.1

“The urban, inner-city heroin epidemics of the 80s and 90s were overwhelmingly male and overwhelmingly minority, and that’s really changed,” said Chris Beyrer, MD, of the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, in an interview. “The current opioid crisis is whiter, it’s more female, it’s more rural and suburban — it’s a different demographic. And in those kinds of communities, “HIV is highly stigmatized,” he added.

On February 5, 2019, the Trump Administration announced plans to address the HIV epidemic in the United States. In his State of the Union Address, then-President Trump pledged to decrease the number of new HIV infections by 75% in 5 years and by 90% in 10 years, effectively ending the epidemic by 2030.4 This proposal, a 4-pillar approach developed by the US Department of Health and Human Services (HHS), was focused heavily on HIV diagnosis, treatment, prevention, and outbreak response.3 The tools, researchers pointed out, are “already at hand” to accomplish this goal.4 The issue, then, lies with city, state, and federal efforts to address the injection opioid epidemic.

According to Dr Beyrer, there is one primary culprit responsible for the shift in the opioid epidemic from its demographics in the 1980s and 1990s to what it looks like today: OxyContin.

“The overprescribing of prescription opiates is really at the heart of this,” he explained. “If you look at the amount of pain prescriptions that were being written, for example, in West Virginia, it was more than enough for every adult in West Virginia to become opioid  dependent. It was extraordinary.”

The addition of pain as a fifth vital sign, coupled with lobbying efforts on the part of the US pharmaceutical industry and OxyContin manufacturer Perdue Pharma in particular, has significantly changed the pain treatment paradigm.

“If you’ve been to a primary care provider for anything in the last several years, you have been asked, ‘Are you in pain today?’ And if you say ‘Yes, I am in pain,’…and rate your pain over a 4, [that is] reported to the physician to start treatment,” Dr Beyrer added.

By 2004, OxyContin had become a primary drug of abuse in the United States.5 By 2009, 1.2 million emergency department visits were being attributed to abuse or misuse of pharmaceutical pain medications,6 reflecting a 5-year increase of 98%. As the US Food and Drug Administration (FDA) moved to respond to soaring rates of addiction and overdose deaths, access to the opioid medications on which so many people had become dependent emerged as a significant challenge.

A reformulated, abuse-deterrent OxyContin was released in 2010; this tamper-resistant formulation included polyethylene oxide (PEO), an inactive polymer that rendered the tablets “harder, more crush-resistant, and more difficult…to prepare for injection,” according to an FDA briefing document.7 At the same time, the agency moved to address how, exactly, OxyContin, Opana ER (oxymorphone hydrochloride, Endo Pharmaceuticals), and other addictive opioid medications were being prescribed in clinical practice. This, according to Dr Beyrer, is what led to the synthetic opioid crisis and the subsequent soaring increase in heroin-involved overdose deaths.

“As we finally understood what was happening [with the opioid crisis] and finally started to have some kind of response and get control of prescribing, the people who were already opioid-dependent and couldn’t get a hold of OxyContin switched over to street-available drugs,” he said. “By the way? OxyContin at its peak on the black market was $50 a pill. A bag of heroin in Baltimore City costs $15.”

Today, a line can be drawn directly from the rise in opioid addiction-fueled, injection drug use to the increase in diagnoses of HIV attributed to injection drug use.3 But because both drug addiction and HIV remain highly stigmatized, each condition — both individually and together — is difficult to treat.

“There are certainly interventions out there, [but] the outcomes of those interventions are still pretty depressing,” said Michael L. Barnett, MD, an assistant professor of health policy and management at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, in an interview. “This is a disorder with very high rates of remission and relapse, so a lot of the focus is on trying to see what we can do to mitigate barriers to accessing medication for opioid use disorder [with] medications [that] are quite safe compared with the alternative.”

There’s a robust body of evidence demonstrating the efficacy of medications for opioid use disorder,8-10 but the barriers to providing these medications are high and include, but are not limited to, physician waivers to prescribe buprenorphine, the lack of training in addiction treatment services offered in medical schools and residency programs, and the idea, according to Dr Barnett, that “addiction medicine is something that other people do and something other people take care of.” And among injection drug users, Dr Barnett added, the current adequacy of infectious disease screening is poor.

“These folks need to be screened for HIV, hepatitis C, and hepatitis B regularly,” he said. “That’s another quality measure that I think we frequently fall short on. Infectious disease physicians are not the ones doing this [treatment],” he added. “Many people with addiction will eventually get hepatitis C. How do we make sure that we’re staying on top of that population?”

Both Dr Barnett and Dr Beyrer highlighted the 2014 to 2015 HIV outbreak in Scott County, Indiana, under the leadership of then-Governor Mike Pence, as a prime example of a perfect, intersectional storm that illustrates what happens when harm-reduction interventions such as needle and syringe exchanges are criminalized.

“In Scott County…needle and syringe exchange, and distributing syringes without a prescription, was a felony with a 2-year sentence,” said Dr Beyrer. “It was illegal to provide services needed for basic public health.”

“Mike Pence…lifted those restrictions for 1 month — just 1 month — just in Scott County. Eventually, they had to be lifted across the state because it turned out that Scott County was not an isolated outbreak but really just 1 of the [outbreaks] that we had identified.”

“There were a lot of new HIV infections in Indiana because there wasn’t really a swift response to that problem,” Dr Barnett added. “There was a more personal-responsibility, law-enforcement angle to the response, which we know is not effective.” 

Thanks to both advances in medical science and large-scale public health campaigns, there is a general public awareness and understanding of HIV. Recent data from large clinical studies have confirmed the concept of “undetectable equals untransmittable,”3 which should have, in theory, contributed to a reduction of the stigma associated with HIV. In many communities, however, that is not exactly the case.

In the White rural and suburban communities where the current opioid crisis has taken hold, HIV remains highly stigmatized — even more so among women, some of whom are mothers living at the intersection of drug use and HIV infection.

“What we’re seeing is that all of these intersecting challenges, beginning with opioid use, are more likely to be happening in families and have an intergenerational component,” noted Dr Beyrer. “Parents [are] using with their adult children, adolescents [are] using, men and women and couples [are] both using and sharing.”

And for women who inject drugs, there’s an additional layer of stigma to contend with. “It’s very [stigmatizing] for women to know how to use; know how to inject and how to handle equipment,” Dr Beyrer explained. “It’s very often the man who uses first, then injects the woman, and that means that her likelihood of having an unsterile injection is higher. There’s a gender dynamic to all of this [as well].”

Regardless of gender, access to antiretroviral therapy (ART) for people who inject drugs is shrouded in controversy in much of the world. In many countries, governmental policies require complete abstinence from illegal drug use before providing ART. Rather than motivating people to seek treatment, it deters people with HIV from seeking treatment.11 These policies are not necessarily mirrored in the United States, but there is still a persistent, sustained shame associated with those who are actively using drugs within the healthcare system.

“What you see is that people don’t want active drug users in their practice,” Dr Beyrer said. “[Physicians] refuse to treat them or they set up a policy where they say, ‘I will treat your HIV as long as you’re clean, but if you start using again, I won’t.’ And in many of these settings, people don’t have a lot of options.”

“All of the issues with disparities in care across race, socioeconomic status, and so on are just as much present in addiction care, if not more so, than for other medical interventions,” Dr Barnett noted. “There’s a big policy focus on what do we do about access to addiction care in rural communities?”

Ensuring that the available resources are not structurally organized around predominantly White communities, or around pathways predominantly used by White patients, is key, according to Dr Barnett. At Harvard, he pointed out, the addiction clinic is located at Brigham and Women’s Hospital in Boston, Massachusetts, and is rife with marble columns, bright high ceilings, and intimidating portraits of White men.

“It’s a place that can seem intimidating for someone who’s not used to being in those spaces,” explained Dr Barnett, “someone who works at night as a janitor or someone who doesn’t speak English. “The Brigham [and Women’s Hospital] can’t change itself, but it could try to invest in addiction treatment in the communities where it’s needed most.”

Taken together, the structural concerns, racial and socioeconomic issues, and state- and federal-level policy issues can paint a grim picture when trying to address these concurrent intersecting epidemics. Reducing injection drug use is paramount to decreasing newly diagnosed cases of HIV, but the general negative attitude toward drug users, and injection drug users in particular, renders these efforts daunting.

“In this particular population where we know that there are these associations [between] HIV and substance use, we have an overwhelming amount of data to show that if you implement the basics of prevention, you can virtually bring an end to the epidemic of injection drug use,” Dr Beyrer said.

Dr Hodder and colleagues (which includes Dr Beyrer) suggested a number of recommended strategies to address the HIV and opioid epidemics.1 First, they wrote, it is essential to diminish stigma for both people living with HIV and people with opioid use disorder. Community-based interventions are essential, as is the commitment of dedicated thought  leaders, for ensuring that people who inject drugs can “receive quality services in a nonjudgmental environment.”

Another strategy is to provide universal healthcare for all people who inject drugs. Only 18% of the estimated 22 million people with substance use disorders were able to receive addiction treatment prior to Medicaid expansion.1 Following the expansion, uninsured hospitalizations associated with substance use disorders decreased from 22% to 14% in the course of 1 year.

A renewed focus on evidence-based approaches, including the discontinuation of the war on drugs and its associated carceral paradigm that emphasizes imprisonment over addiction treatment, the inclusion of primary care clinics as touchpoints for patients that can provide treatments such as HIV pre-exposure prophylaxis (PrEP), methadone, and buprenorphine, and a renewed focus on research to develop both better treatments for opioid use disorder and differentiated care models will also go a long way toward facilitating a dual reduction in HIV diagnoses and opioid use.

“The good news is that we have a toolkit that is really effective at preventing HIV and viral hepatitis spread among people who inject drugs,” said Dr Beyrer. “This is not rocket science; it’s the basics of public health prevention. It works, it’s effective, it’s cheap, and it’s an alternative to mass incarceration.”

“It really is the responsibility of everybody who provides healthcare to get educated about this and to become not just a provider, but also an advocate, for policies that work and are evidence-based. That’s what we’re supposed to be doing,” he added. “We’re supposed to be scientists.”

References

1. Hodder SL, Feinberg J, Strathdee SA, et al. The opioid crisis and HIV in the USA: deadly synergies. Lancet. 2021;397(10279):1139-1150. doi:10.1016/S0140-6736(21)00391-3

2. Sullivan PS, Johnson AS, Pembleton ES, et al. Epidemiology of HIV in the USA: epidemic burden, inequities, contexts, and responses. Lancet. 2021;397(10279):1095-1106. doi:10.1016/S0140-6736(21)00395-0

3. Fauci AS, Redfield RR, Sigounas G, Weahkee MD, Giroir BP. Ending the HIV epidemic: a plan for the United States. JAMA. 2019;321(9):844-845. doi:10.1001/jama.2019.1343

4. Lerner AM, Fauci AS. Opioid injection in rural areas of the United States: a potential obstacle to ending the HIV epidemic. JAMA. 2019;322(11):1041-1042. doi:10.1001/jama.2019.10657

5. Van Zee A. The promotion and marketing of oxycontin: commercial triumph, public health tragedy. Am J Public Health. 2009;99(2):221-227. doi:10.2105/AJPH.2007.131714

6. US Food and Drug Administration. Timeline of selected FDA activities and significant events addressing opioid misuse and abuse. Updated March 30, 2021. Accessed June 15, 2021. https://www.fda.gov/drugs/information-drug-class/timeline-selected-fda-activities-and-significant-events-addressing-opioid-misuse-and-abuse

7. FDA Advisory Committee Meeting. September 10-11, 2021 joint meeting of the drug safety and risk management advisory committee and the anesthetic and analgesic drug products advisory committee meeting announcement. OxyContin® (oxycodone hydrochloride) extended-release tablets. NDA 022272. Postmarketing requirement briefing document. Published September 10-11, 2020. Accessed June 15, 2021. https://www.fda.gov/advisory-committees/advisory-committee-calendar/september-10-11-2020-joint-meeting-drug-safety-and-risk-management-advisory-committee-and-anesthetic

8. Bell J, Strang J. Medication treatment of opioid use disorder. Biol Psychiatry. 2020;87(1):82-88. doi:10.1016/j.biopsych.2019.06.020

9. Haight BR, Learned SM, Laffont CM, et al; RB-US-13-0001 Study Investigators. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2019;393(10173):778-790. doi:10.1016/S0140-6736(18)32259-1

10. Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for management of opioid use disorder. Am J Health Syst Pharm. 2019;76(15):1097-1103. doi:10.1093/ajhp/zxz105

11. Avert.org. People who inject drugs, HIV and AIDS. Updated October 10, 2019. Accessed June 15, 2021. https://www.avert.org/professionals/hiv-social-issues/key-affected-populations/people-inject-drugs.

This article originally appeared on Infectious Disease Advisor

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