HIV and Substance Use Disorders

Summary

The intricate nature of SUD underscores the necessity for specialized expertise in managing each unique SUD. However, amid the current deficit in such expertise and the absence of tailored treatment guidelines, there are actionable steps at a fundamental level. This involves acknowledging the nuanced intersection of HIV and substance use and subsequently integrating HIV assessment within SUD disciplines and addressing SUD within HIV disciplines to reduce care silos. This integrated approach ensures a holistic response to each epidemic—HIV and SUD—by recognizing and addressing their interconnected challenges from the outset of assessment, through treatment, and into management.

Background

The Current state of the problem

Substance Use Disorder and HIV

An estimated 11.1% of people with HIV (PWH) have a diagnosis of substance use disorder (SUD).¹ HIV may be transmitted by sharing injection drug equipment and high-risk sexual behaviors associated with substance use (e.g., condomless or Pre pre-exposure prophylaxis (PrEP)-less sexual intercourse, multiple partners, transactional sex, or commercial sex work).² Adults and adolescent persons who inject drugs (PWID) accounted for 8% of new HIV diagnoses in the United States in 2021, increasing since 2017.³ Importantly, clusters of HIV outbreaks have occurred among PWID; for example, between 2014–2015, an HIV outbreak related to injection drug use in Scott County, Indiana, where 181 individuals were newly diagnosed.⁴ Similarly, from 2015 through 2018, the communities of Lawrence and Lowell, Massachusetts experienced an outbreak of HIV among 129 PWID⁵, and in 2018–2019, Cabell County in West Virginia witnessed an outbreak among 14 PWID.⁶ These outbreaks occurred even in communities with comprehensive harm reduction services, signifying important public health implications related to identifying drug-related outbreaks and the rapid implementation of screening, linkage to care, and harm reduction services to break chains of transmission.⁷ Further, persons with untreated SUD may have difficulty adhering to antiretroviral therapy (ART)¹ and often receive inadequate medical care, partly due to the traditional separation of HIV care and substance use services.

Substance Use Disorders among PWH and Populations at Risk for HIV

Opioid Use Disorder: Background, Epidemiology and Treatment

Opioid misuse and opioid use disorder (OUD) are associated with poor ART adherence⁸ and HIV transmission via shared injection equipment associated with parenteral opioid (heroin, fentanyl, and/or its derivatives) use or through unprotected sexual intercourse while using opioids.² There are three medications for opioid use disorder (MOUD): buprenorphine, extended-release naltrexone (XR-NTX), and methadone.⁹ Buprenorphine is a partial μ-receptor opioid-agonist approved for moderate to severe Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) OUD. Formulations of buprenorphine include daily sublingual tablets (Subutex^®), buccal film (Belbuca^®), extended-release subcutaneous monthly injection (Sublocade^®), and weekly and monthly injections (Brixadi^®). Buprenorphine and naloxone coformulations are available, including buccal film (Suboxone^®) and sublingual tablets (Zubsolv^®).¹⁰ XR-NTX (Vivitrol^®), the only μ-receptor antagonist, is prescribed as an intramuscular injection every 28 days following a required 7-day period of opioid abstinence to avoid precipitated withdrawal.⁹ Lastly, methadone is a long-acting full μ-receptor agonist that can only be prescribed within an authorized opioid treatment program, thus limiting the accessibility of this medication.⁹

Alcohol Use Disorder: Background, Epidemiology and Treatment

An estimated 30–50% of PWH have an alcohol use disorder (AUD),¹¹ which increases the risk of poor linkage to HIV care and ART initiation in PWH, decreases adherence to ART and contributes to poor HIV treatment outcomes, including lack of viral suppression.¹²

Three medications are FDA-approved for the treatment of DSM-5 moderate to severe AUD: acamprosate, disulfiram, and naltrexone (oral daily pills and monthly injections of XR-NTX). The American Psychiatric Association recommends that either naltrexone or acamprosate be offered as first-line treatment. Acamprosate is more efficacious in promoting abstinence,¹³ while XR-NTX is more efficacious in reducing heavy drinking and total alcohol consumption.¹⁴ Despite this efficacy, less than 9% of patients who undergo any form of AUD treatment receive pharmacotherapy.¹⁴ Additionally, motivational enhancement therapy (MET), cognitive behavioral therapy (CBT), and 12-step programs, such as Alcoholics Anonymous, are helpful alone or in combination with medication to reduce alcohol use for persons with AUD.¹⁴

Stimulant Use Disorder: Background, Epidemiology and treatment

Stimulant use has negative implications for HIV prevention and treatment.¹⁵ There are no current FDA-approved medications for stimulant use disorder (StUD), yet there are some medications, such as bupropion, modafinil, and topiramate, that may be helpful for cocaine and amphetamine-type stimulant use disorder per current American Society of Addiction Medicine and American Academy of Addiction Psychiatry Stimulant Use Disorder Guidelines.¹⁶ The most effective form of treatment that should be incorporated in any plan for stimulant use disorder thus far is contingency management (CM),¹⁷ where participants receive rewards or incentives for achieving reduced stimulant use or abstinence. CM has been shown to improve adherence to ART¹⁸ and viral suppression in PWH who use drugs.¹⁹ CM plus a community reinforcement approach led to an increased number of abstinent patients and was more efficacious than CBT, non-contingent rewards, and 12-step program plus non-contingent rewards.²⁰ CM, however, may present multiple barriers for clinicians (e.g., logistics of maintaining an adequate supply of behavior reinforcers) and barriers for clients (e.g., transportation, housing instability, frequent appointments, and/or drug screens), leading to referral to specialty care.²¹ The FDA has approved Dynamicare, a CM mobile application with live assistance²² that is individualized to support people with StUD (See below under mobile health).

Benzodiazepine Use Disorder: Background, Epidemiology and treatment

Persons who inject drugs (PWID) and use benzodiazepines may engage in risky behaviors including paying for sex, sharing injection equipment, increasing injection frequency, and injecting more heroin and amphetamines.²³ Further, benzodiazepines’ impact on ART adherence and the potential cognitive implications for PWH is understudied.²⁴ Lastly, some benzodiazepines (e.g., alprazolam, diazepam) are cytochrome P 3A4 substrates and, when combined with ritonavir and cobicistat-boosted ART, may result in prolonged half-lives and increased concentrations that may cause enhanced and prolonged sedating effects.²⁵

There is no specific pharmacotherapy to treat benzodiazepine dependence. Psychological interventions (e.g., CBT) with stepwise withdrawal may be beneficial in reducing benzodiazepine use over short periods. Group or individual psychotherapy techniques may be more useful in outpatient withdrawal treatment.²⁶

Club drugs: Background and treatment

The use of club drugs, including methylenedioxymethamphetamine (MDMA), gamma hydroxybutyrate (GHB), ketamine, mephedrone, inhaled nitrate (‘poppers’), and phosphodiesterase inhibitors (PDE5), reduces ART adherence in PWH.²⁷ Further, in persons without HIV, club drug use increases risk-taking behavior and risk of HIV transmission.²⁷ Lastly, due to interactions with the cytochrome P oxidase 450 (CYP450) system²⁷ or PDE5,²⁸ overdoses from club drugs (e.g., MDMA, GHB, ketamine) have been reported.

There are no recommended pharmacotherapies to treat club drug use. Current treatment is limited to behavioral interventions developed for other SUD.²⁷

Discussion: What can be done?

Treatment of SUD in People with HIV can Improve HIV outcomes

Treatment of underlying SUDs can improve outcomes in PWH (See Table 1 for Diagnostic Measures and Table 2 for SUD treatments). For OUD, all three MOUDs are effective in treating opioid craving, relapse, and overdose,⁹ and maintenance of MOUD is associated with reduced HIV risk behaviors,^29,30 improved retention in HIV treatment, improved ART adherence, achieving and maintaining viral suppression,^31–33 and reduction in HIV transmission.³⁴ XR-NTX has been demonstrated to reduce alcohol consumption and improve viral load suppression in PWH with AUD who were being released from prisons or jails into the community.^35,36 Medication treatment for other SUD is limited, especially concerning HIV outcomes, and remains a major gap in HIV care.³⁷

Table 1 -.

Substance Use Disorder Screening and Diagnostic Assessments (Adults)

Pre-screening test
NIDA Single Question Screening test for Drug Use	“How many times in the past year have you used an illegal drug or used a prescription medication for non-medical reasons (for example, because of the experience or feeling it caused)?” Responses to one or both should be followed up with a full screen
Drug Abuse Screening Test (DAST-1)	“In the last 12 months, have you used drugs other than those required for medical reasons?”. Positive response should be followed up with a DAST-10 (also available in Spanish)
Alcohol Use Disorders Identification Test-Concise (AUDIT-C)	“How often do you have a drink containing alcohol?”; “How many standard drinks containing alcohol do you have on a typical day?”‘ “How often do you have 4 or more drinks on one occasion?”. Positive responses should be followed up with a 10-question AUDIT assessment
Substance Use Brief Screen (SUBS)	“How many times in the past year have you used a recreational drug or used a prescription medication for non-medical reasons?”. Positive responses should be followed by a full screen.
Older Adult Brief Screen (Age 60 and older)	“How often do you have a drink containing alcohol?”; “How many standard drinks containing alcohol do you have on a typical day of drinking?”; ‘How often do you have 4 or more drinks on one occasion?”; “How many times in the past year have you used an illegal drug or used a prescription medication for non-medical reasons (for example, because of the experience or feeling it caused)?”‘; “Have you used any cannabis over the past six months?”. Positive responses should be followed by ASSIST-LITE full screen.
Rapid Opioid Use Disorder Assessment (ROUDA)	8-question diagnostic tool to assess DSM-5 moderate to severe OUD provides diagnosis in 2–4 minutes with a score of 3 or greater and can be given by non-clinicians. Captures long-term and short-term remission
Rapid Stimulant Use Disorder Assessment (RSUDA)	8-item diagnostic tool to assess DSM-5 moderate to severe stimulant use disorder diagnosis in 2–4 minutes with a score of 3 or greater and can be given by non-clinicians. Captures long-term and short-term remission
Full screening test
Alcohol Use Disorder Identification Test (AUDIT)	10-question screening tool to assess risky alcohol use across age, cultures, and gender
Alcohol, Smoking, and Substance Abuse Involvement Screen Test (ASSIST)	8-question assessment of risky substance use covering alcohol, amphetamine-type stimulants, cannabis, cocaine, hallucinogens, inhalants, opioids, sedatives, tobacco
ASSIST-LITE	6-question assessment of commonly used substances, including alcohol, cannabis, opioids, sedatives, stimulants, tobacco (simplified version of ASSIST)
Tobacco, Alcohol, Prescription Medication, and Other Substance Use Tool (TAPS)	An adaptation of ASSIST-LITE, this tool is a two-stage screen for commonly used substances (screening and brief intervention)
Drug Abuse Screening Test (DAST-10)	10-item self-reported instrument that assesses drug use over the preceding 12 months (excludes alcoholic drinks)
The Cannabis Use Disorders Identification Test (CUDIT-R)	8-item tool used to assess for cannabis use disorder

Pre-screening and full screening instruments for substance use disorder. Adapted from [SBIRT: Screening, Brief Intervention and Referral to Treatment. New York State Office of Addiction Services and Supports. Accessed November 30, 2023. https://oasas.ny.gov/sbirt and Di Paola et al. Validation of Two Diagnostic Assessment for Opioid and Stimulant Use Disorder for Use by Non-Clinicians. Psych Res Clin Pract. 2023;5:78–83; doi: 10.1176/appi.prcp.20230022]

Table 2-.

Substance Use Disorder Treatments

Substance use disorder	Treatment	ART Interactions
Alcohol use disorder
Acamprosate	666 mg PO three times a day or 333 mg PO three times a day for patients with CrCl 30–50 mL/min	None
Disulfiram	250 mg PO once daily	Use caution when prescribing ART that contain ethanol or propylene glycol (e.g., FPV, LPV/r, RTV)
Naltrexone	50–100 mg PO once daily or 380 mg intramuscular suspension every 28 to 30 days	None
Opioid use disorder
Buprenorphine	Individualize buprenorphine doses based on patients’ prior opioid use. Suggested dose range is 4–32 mg sublingually tablet or film, once or twice daily; subcutaneously (Sublocade 300 mg once monthly for two months, then 100 mg monthly maintenance dose); Weekly or monthly injections, Brixadi (multiple dose formulations)	Potential interactions with ART regimens that are CYP inhibitors or inducers
Extended-release naltrexone	380 mg intramuscular suspension every 28 to 30 days	None
Methadone (oral daily	Individualized dosed regimens; patients who received higher doses (e.g. >100 mg) are more likely to remain in treatment	Potential interactions with ART regimens that are CYP inhibitors or inducers
Sedative use disorder (Benzodiazepines)
	Cognitive behavioral therapy, Group or individual psychotherapy, Slow supervised taper	N/A
Stimulant use disorder
	Medications not FDA approved but available. (Refer to the ASAM/AAAP guideline) Cognitive behavioral therapy, Contingency management, Motivational interviewing	N/A

FPV=fosamprenavir, LPV/r=lopinavir-ritonavir, RTV=ritonavir, CYP=cytochrome P450, mg=milligram, mL=milliliters, min=minute, PO=by mouth, CrCl, creatinine clearance, ART=antiretroviral therapy

Substance use disorder treatments and HIV antiretroviral interactions. Adapted from [Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. HIV.gov. Updated June 3, 2021. Accessed November 30, 2023. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/substance-use-disorders-and-hiv]

Pre-exposure Propylaxis (PrEP) for People Who Use Drugs Who are at Risk for HIV

Despite International AIDS Society (IAS)-USA recommendations for PrEP among PWID and who use drugs (PWUD) with sexual risk, global PrEP implementation has been slow.³⁷ Increasing access via integrating PrEP into MOUD programs is an additional opportunity to engage PWID and PWUD in HIV prevention.³⁸ Low-risk perception³⁹ and poor access to PrEP⁴⁰ may partly explain low utilization rates in addition to physicians’ explicit or implicit bias against prescribing PrEP for PWID, mainly due to suspicion of medication non-adherence.⁴⁰ New PrEP delivery advances may help address these adherence concerns. Long-acting injectable (LAI) cabotegravir PrEP, injected every two months, has demonstrated superiority in preventing HIV compared to daily, oral PrEP and is now recommended for MSM, transgender, and cis-women.⁴¹ Reducing provider bias and overcoming structural barriers to expand LAI PrEP access to all at risk for HIV are critical in engaging PWID and PWUD in highly effective biomedical interventions. Lastly, nearly one-third of PWID are also at risk for HIV via sexual behaviors⁴² and should be screened for bacterial sexually transmitted infections.

Ending the HIV Epidemic via SUD treatment

Ending the HIV Epidemic (EHE) is the US national plan for HIV aiming to reduce new HIV infections by 75% by 2025 and 90% by 2030 through four key strategies: (1) universal HIV testing; (2) rapid treatment of new HIV diagnoses and ensuring viral suppression, (3) prevention of HIV via provisions of rapid Pre-exposure prophylaxis (PrEP) for those who test HIV negative and syringe services for PWID, and (4) responding rapidly to new HIV outbreaks by providing needed preventive and treatment services.⁴³ However, the EHE plan did not include specific guidance or goals targeted for PWUD who are at high risk for HIV acquisition or transmission. Further, the EHE plan relies on persons to attend traditional brick-and-mortar clinics, overlooking barriers to care that can be exacerbated in settings where care is not integrated, as patients often have to go to multiple providers for different care needs.⁴⁴ PWUD are, therefore, a high-risk group that would benefit greatly from interventions that reduce barriers to accessing care. In order to address this important limitation in the EHE initiative, the National Institute on Drug Abuse (NIDA) issued a Note of Special Interest (NOSI) in December 2022 to support research that expands the EHE scope to include PWUD who are living with, or at risk for, HIV.⁴⁵

HIV and Substance Use Disorder Integrated Care Models

Given the overlapping barriers that hinder access to healthcare for PWUD and PWH, there is a substantial need for integrating care for SUD and HIV.⁴⁶ Indeed, the National Academies of Science, Engineering, and Medicine (NASEM) identified opportunities to integrate care for PWH and OUD (which could also be applied to AUD and stimulant use disorder), including removing limits on harm reduction services such as syringe services programs (SSPs), removal of state-level prior authorization policies to prescribe buprenorphine, elimination of the DATA DEA X-Waiver, removal of same-day billing restriction for behavioral and physical healthcare, expansion of Medicaid health insurance in states that have not already done so, reduction of stigma, and inclusion of integrated care into medical education.^{47, 48} As of this NASEM report, the requirement of an X-waiver has been removed in order to prescribe buprenorphine, which is an improvement, although that has only led to a modest increase in the number of patients receiving buprenorphine.⁴⁹ Additionally, the Medication Access and Training Expansion (MATE) Act, which requires applicants for a new or renewed DEA license to complete at least eight hours of training on treating and managing patients with OUD or other SUD, can contribute to the expansion of providers who can prescribe buprenorphine but may also not necessarily lead to patients receiving the medication. Unfortunately, integrated care models have largely focused on brick-and-mortar clinical settings, which may not be a realistic option for many PWH with concomitant SUD.^37,47

Brick-and-mortar facilities

In these traditional settings, best practices recommend that patients be offered routine screening for both SUD and HIV testing, with the provision of PrEP or ART as appropriate.³⁷ In addition, due to the increased risk of acquiring bacterial sexually transmitted infections (STI) among PWUD,⁵⁰ the provision of STI screening should also be offered in these settings. Further, all PWH with OUD or AUD should be offered medication treatment.³⁷ Next, all healthcare professionals who provide care for PWH should be trained to identify, screen, and treat SUDs, regardless of their training background.^37,51 It is insufficient to refer patients to addiction medicine specialists or psychiatrists simply. Instead, PWH who are diagnosed with SUDs should be assessed for treatment readiness in-clinic by providers and be offered medications to reduce symptoms of withdrawal.⁴⁷

Access to SUD treatment, particularly MOUD, has often been challenging for PWUD in brick-and-mortar settings due to factors such as stigma,⁵¹ incarceration, and lack of transportation.³⁷ As such, brick-and-mortar facilities should prioritize expanding staff SUD training, utilizing peer navigators, and integrating HIV and SUD care.³⁷

Mobile health clinics

In response to the structural barriers that prevent optimal SUD service delivery in brick-and-mortar facilities, mobile health clinics (MHC) may bridge this gap by meeting patients “where they are”.⁵² MHC brings clinical services to the community level, providing health services in locations and times that may not be available in traditional healthcare facilities. MHC models can overcome transportation issues, health insurance, stigma, and discomfort around traditional healthcare settings.⁵² MHC may most benefit justice-involved persons, rural communities, transgender persons, women, unhoused, and uninsured persons.⁵² Despite increased interest,⁵³ MHCs face limited pharmacy access since mobile retail pharmacies are either illegal or heavily regulated within the United States, requiring an established opioid treatment program (OTP). Thus, to allow MHC to be truly successful in meeting PWUD where they are, state and/or federal-level legislation allowing for the provision of PrEP and ART within mobile retail pharmacies and DEA approval of buprenorphine in non-traditional settings must be permitted.⁵²

Prisons/jails

Justice-involved persons have higher rates of HIV and SUD than the general population yet are often not provided with sufficient care for these two conditions in US carceral settings.⁵⁴ For instance, justice-involved persons often are unable to access testing treatment or PrEP care.⁵⁴ Expanding integrated SUD and HIV treatment and prevention services within these settings is paramount. Further, implementation of evidence-based preventive care, including PrEP and MOUD, prior to prison release for people with OUD is critical for improving individual and public health outcomes. Further, post-release linkage to SUD and HIV care is vital in order to ensure that patients continue to have access to ART, PrEP, and SUD treatment and remain retained in care.⁴⁷

Harm reduction programs

Harm reduction program services provide syringe exchange and sterile injection equipment (e.g., water, syringes, cotton), naloxone, fentanyl test strips, barrier protection, and basic wound care⁵⁵ are well-positioned to provide integrated care for PWUD with HIV or at risk for HIV. In addition to SUD care and screening, they can be utilized to provide rapid HIV, HCV, bacterial STI testing, and PrEP. The Veterans Health Administration (VHA) syringe services program (SSP), an excellent example, engaged over 400 Veterans and dispelled confusion around legal considerations regarding the federal purchase of syringes. There are now 10 successfully implemented SSPs within the VHA, with 12 more “in progress”. These programs have distributed 10,000 syringes, 2,500 fentanyl test strips, 50 wound care kits, and 45 safer sex kits while providing HIV and HCV testing.⁵⁶ Unfortunately, outside of the VHA, community harm reduction programs have not been legalized in every state.

Mobile device health

Mobile device health (mHealth) has the potential to provide holistic, patient-centered, integrated care for PWUD with HIV and at-risk for HIV. For example, a pilot HIV and Hepatitis education initiative was associated with increased and sustained improvements in knowledge regarding HCV and HIV transmission and risk behaviors in participants with OUD.⁵⁷ Further, mHealth applications are integrating HIV and SUD, such as ART-CHESS (Antiretroviral Therapy-Comprehensive Health Enhancement Support System)⁵⁸ for people with HIV and OUD and PositiveLinks for people with HIV and PWUD application, which has shown significant improvement in HIV virologic suppression.⁵⁹ DynamiCare Health mobile app is feasible and acceptable for CM related to AUD, OUD, cannabis, nicotine, and stimulant use disorder and is now FDA-approved to provide incentivized mobile app provided CM treatment for SUDs.²² Lastly, the CARE+ Corrections for PWH, recently released to the community from carceral settings, improved the proportion of participants virologically suppressed.⁶⁰ For PWUD at risk for HIV, a mHealth approach to remind individuals to use PrEP and educate them on HIV risk reduction is feasible and acceptable.⁶¹

Key points:

• Untreated substance use disorder increases the risk for HIV acquisition and leads to poor HIV outcomes in people with HIV

• Treatment of concomitant substance use disorder reduces the risk of HIV transmission in persons at risk for HIV and improves HIV outcomes in people with HIV

• Persons with substance misuse and substance use disorders should be screened for HIV and be offered pre-exposure prophylaxis (PrEP)

• People with HIV should be screened for substance misuse and substance use disorders

• Screening for substance misuse and substance use disorders should be integrated into HIV prevention and treatment, substance use disorder treatment, and harm reduction care settings

Synopsis:

Over 1.2 million Americans aged 13 and older have been diagnosed with HIV. While HIV incidence has been declining since 2017, the risk of HIV acquisition and transmission persists among persons who use drugs via injection drug use and unprotected sexual intercourse associated with substance use. Untreated substance use disorder is associated with poor adherence to HIV antiretroviral therapy, poor HIV outcomes, and increased risk for HIV acquisition. Herein, we describe the intertwined syndemic of HIV and substance use disorder, as well as treatment strategies and evidence-based public health efforts to engage and retain persons who use drugs into care.

Clinics Care Points.

• People with SUD should be tested for HIV and offered PrEP if negative.

• HIV sex risk behaviors should be assessed in all PWUDs, and PrEP (oral or long-acting injectable) should be offered.

• PWH should be screened for SUD, and ART integrated with their treatment for SUDs.

• Mobile health clinics and mHealth are opportunities to engage people in care without traditional structures of care and improve HIV clinical outcomes.

• Buprenorphine and other forms of MOUD and other SUD treatments should be expanded beyond traditional brick-and-mortar facilities.

• Harm reduction services should be integrated into clinical settings.

• LAI-ART may be offered to PWH who are already taking LAI forms of medication for SUD.