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Abstract

New human immunodeficiency virus (HIV) cases related to injection drug use (IDU) in the United States increased between 2016 and 2022. The uptake of preexposure prophylaxis (PrEP) is exceedingly low in persons who inject drugs (PWID) despite its efficacy to prevent HIV. There are multilevel barriers in the PrEP care cascade for PWID. We need a combination of effective HIV prevention strategies, including PrEP, treatment for substance use disorder, and syringe services programs (SSP) to reverse the trend. A major challenge is the lack of knowledge and skills in harm reduction practices and addiction care in the infectious disease (ID) workforce. ID clinicians could benefit from education in harm reduction and addiction, including taking on the responsibility of prescribing buprenorphine or navigating the resources for it. Addiction clinicians could benefit from education on PrEP and related program implementation knowledge. Both specialties need to comprehensively evaluate and address the risks for HIV acquisition in PWID. We should create integrated clinical programs between ID and addiction. We should improve HIV screening for hospitalized PWID. We should expand low-barrier integrated clinics with flexible hours, walk-in appointments, same-day PrEP starts, and collocated laboratory and pharmacy services. Other entities that could provide integrated care include substance detoxification and rehabilitation programs, SSPs, opioid treatment programs (OTP), community pharmacies, and mobile health clinics. Long-acting injectable PrEP for PWID is an attractive option for HIV prevention, but robust implementation programs are necessary for roll-out. We still need to address upstream barriers to care for PWID, including stigma and health disparities. We need to continue to advocate for policy changes and funding for SSPs and OTPs to provide comprehensive HIV prevention.

Keywords

addiction harm reduction HIV MOUD PrEP PWID SSP

Background

Injection drug use (IDU) related new human immunodeficiency virus (HIV) cases in the United States (US) increased from 2016 to 2022,¹ and HIV prevention strategies for persons who inject drugs (PWID) are urgently needed. In 2022, 7% of newly diagnosed HIV cases were attributed to IDU.² Despite that, oral daily preexposure prophylaxis (PrEP) reduced HIV acquisition by 49% in PWID,³ studies show that only 0%–3% of PWID took oral PrEP^4,5 and demonstrated multilevel barriers to PrEP uptake.^4,6,7 We need to significantly improve the PrEP care cascade in PWID.^4,8

While it is critical to improve PrEP uptake in PWID, we also need to increase the uptake of harm reduction interventions and addiction care. They are critical to prevent HIV in PWID and have been underutilized by the infectious disease (ID) workforce. One study showed that only half of 196 ID fellowship trainees received formal didactics around care of PWID, and medications for opioid use disorder (MOUD) were discussed in only one-third of these didactics.⁹ Another study reported that among 534 ID physicians, 70% routinely cared for PWID, but only 45% provided safe injection practice counseling. Lack of training was a main reason for not providing the counseling.¹⁰

This narrative review focuses on harm reduction and addiction care as effective non-antiretroviral HIV prevention strategies. It provides a primer on harm reduction practices and non-antiretroviral (ART) HIV prevention strategies in PWID. Subsequently, it reviews the barriers to addiction care, harm reduction services, and PrEP. Finally, it proposes strategies to integrate ID and addiction education and clinical care for comprehensive HIV risk assessment and prevention.

Methods

The author discretionarily selected articles highly relevant to the US substance use epidemic and HIV prevention in PWID and synthesized findings. In addition, abstracts from the Conference on Retroviruses and Opportunistic Infections¹¹ and Association for Multidisciplinary Education and Research for Substance Use and Addiction¹² meetings in 2023–2024 were reviewed for inclusion. Data from the Centers for Disease Control and Prevention (CDC) and other government websites were reviewed and cited accordingly.

Harm reduction principles

Harm reduction is central to addiction care, as the brain disease model of addiction views addiction as a chronic, relapsing-remitting disease.¹³ Harm reduction first tries to identify and understand the negative consequences of substance use. It then focuses on modifying the harms, rather than stopping drug use.^14,15 Arose from the responses to hepatitis B and HIV outbreaks in Europe in the 1980s, it was initially controversial in the US. It became more accepted amidst surging overdoses and substance-related morbidities.¹⁶

Harm reduction principles were also defined for health conditions other than substance use disorders (SUD).¹⁴ Using harm reduction principles for non-SUD conditions may help destigmatize the harm reduction movement and SUD. These principles are humanism, pragmatism, individualism, autonomy, incrementalism, and accountability without termination. Common health conditions utilizing harm reduction principles include diabetes^17,18 and tobacco smoking^19,20 (Table 1). Harm reduction is not considered passive or enabling. To the contrary, it facilitates mutual engagement between individuals and their clinicians toward common goals.^21,22 Individuals and clinicians agree on specific, measurable, achievable, relevant, incremental goals within a specified time. When there are setbacks in achieving goals, there is accountability for patients, but they and clinicians examine the barriers to the goals and design interventions iteratively. There is no patient abandonment or termination of the relationship if goals are not met.

Table 1.

Harm reduction approaches for substance use disorder (SUD), diabetes, and tobacco smoking.

Health condition	SUD	Diabetes	Tobacco smoking
Common complications	Overdose; withdrawal; infectious complications	DKA/HHS; diabetic foot infection; cardiovascular diseases	COPD; cardiovascular diseases; cancer
Traditional goal	Abstinence from substances	Diabetes control	Smoking cessation
Sample harm reduction goals*	Decrease the use of substances; carry naloxone or have someone monitor while using substances to prevent overdose; safe injection practice to prevent infectious complications; ongoing engagement with treatment	Realistic lifestyle modification: change to diet drinks; reduce high glycemic index food to a certain frequency and/or amount; exercise certain amount each week to reduce an agreed amount of weight in a set time	Reduce daily number of cigarettes to an agreed number; consider products that do not contain tar, for example, electronic cigarettes

Harm reduction goals are person-centric and often vary by individual. Some common harm reduction goals are listed.

COPD, chronic obstructive pulmonary disease; DKA, diabetic ketoacidosis; HHS, hyperglycemic hyperosmolar state.

Non-ART HIV prevention strategies in PWID

MOUD and syringe service programs (SSP) together have curbed HIV outbreaks and reduced the HIV seroprevalence.²³ Table 2 summarizes the effectiveness of HIV prevention from MOUD and SSP. Overdose prevention centers (OPC), or supervised injection facilities, are safe and cost-effective to prevent HIV transmission.^24–30 This review excluded the discussion of OPC because only two legally sanctioned OPCs exist in the US.^28–30

Table 2.

HIV risk reduction among PWID through prevention strategy.

Prevention strategy	PrEP*	Methadone^{+ !}	SSP⁺
Risk reduction	49% overall; 74% for those with detectable drug levels	54% in unadjusted analyses; 40% in adjusted analyses	34%

Data derived from the only clinical trial of PrEP in PWID.

Data derived from meta-analysis.

There is no direct data on incident rate reduction with the use of buprenorphine.

HIV, human immunodeficiency virus; PrEP, preexposure prophylaxis; PWID, persons who inject drugs; SSP, syringe services programs.

MOUD as HIV prevention

There are three MOUDs approved by the Food and Drug Administration: buprenorphine, methadone, and naltrexone (Table 3). Most studies on MOUD and HIV prevention were performed with methadone, because it has been used for decades. In a meta-analysis, methadone was associated with a reduction of risk for incident HIV by 54% in unadjusted analyses and 40% in adjusted analyses.³¹ There are no studies on the reduction of HIV incidence with the use of buprenorphine. Available studies suggest that PWID taking buprenorphine reduced risky injection behaviors but not risky sexual behaviors.^32,33

Table 3.

Comparisons between the three FDA-approved MOUDs.

Factors to consider	Buprenorphine	Methadone	Naltrexone
Effect on opioid receptors	Partial agonist	Full agonist	Antagonist
Ceiling for respiratory suppression	Yes	No	NA
OUD treatment	First-line	First-line	Highly selected patients
Prescription	Any clinician	Only dispensed (not prescribed) in OTPs	Any clinician
Administration	Taken on own	Directly observed in OTPs	Taken on own
Pharmacological consideration	Precipitated withdrawal	QT prolongation	Not to be used with opioid analgesics
PDMP record	Yes	No*	No
Street value	Yes	Yes	No

Rarely, when methadone is prescribed for chronic pain, it is reported by a pharmacy to the PDMP.

FDA, Food and Drug Administration; MOUD, medication for opioid use disorder; NA, not applicable; OTP, opioid treatment program; OUD, opioid use disorder; PDMP, prescription drug monitoring program.

Clinical pearls about MOUD

In a large observational study, only methadone and buprenorphine were associated with a reduced risk of opioid overdose or opioid-related morbidity compared to naltrexone, inpatient/residential detoxification, or behavioral interventions.³⁴

Methadone can only be dispensed in federally regulated opioid treatment programs (OTP), also known as methadone clinics. Because it is dispensed from OTPs, it is not reported by pharmacies to the prescription drug monitoring programs (PDMP). Individuals visit OTPs for daily directly observed methadone therapy until they earn a varying number of days of methadone take-home doses. The highest allowed take-home methadone is 28 days worth.^35,36

Buprenorphine is the cornerstone of opioid use disorder (OUD) treatment outside of OTPs. It offers overdose prevention because of the ceiling effect for opioid-related respiratory suppression. In December 2022, the DATA 2000 waiver (X waiver) requirement to prescribe buprenorphine was eliminated,³⁷ and any licensed practitioner can prescribe it. However, there remains widespread reluctance to prescribe buprenorphine.^38,39 A common concern is precipitated opioid withdrawal. There are numerous dosing protocols to reduce the risk of precipitated withdrawal.^40,41 Once individuals successfully initiate buprenorphine, they can choose to use weekly or monthly injectable formulations of buprenorphine for long-term therapy.

It is important to note that while many PWID may eventually choose to take MOUD, some PWID do not intend to take them. For some PWID, abstinence from substances is not a goal. Harm reduction should be the goal to care for these PWID.

SSP as HIV prevention

SSPs are unique to PWID as they are access points to healthcare, in addition to syringe exchanges. SSPs were endorsed by the World Health Organization (WHO)⁴² and the CDC⁴³ for HIV prevention. In the most recent meta-analysis, SSPs were associated with a 34% HIV risk reduction.⁴⁴

Many SSPs provide testing for HIV, viral hepatitis, and STIs, as well as offer PrEP. In addition to needles and syringes, SSPs offer supplies for safer consumption of substances and education for overdose prevention and safe injection. Lastly, SSPs also provide varying degrees of medical care, ranging from wound care, urgent care, to full-spectrum primary care.^45,46

SSPs are natural venues to provide MOUDs. Studies show interests from PWID to initiate buprenorphine in SSPs⁴⁷ and implementation models of buprenorphine treatment based in SSPs.^48,49 There are also considerations for SSPs to provide methadone, which will require relaxation of methadone regulations.⁴⁹

Current challenges in preventing HIV in PWID

There are multilevel barriers to access MOUD,^50–55 addiction treatment, ^55–57 and SSPs^58–60 for PWID. These barriers include stigma, geographic^56,60 and racial/ethnic^52,59 disparities, structural violence,⁶¹ medication prior authorization, same-day billing restrictions from different specialties, federal regulation limiting sharing of substance use information, and funding limitations.⁵³

Barriers to MOUD

Racial/ethnic disparity is particularly prominent, with White individuals having greater access to MOUD, especially buprenorphine.^52,62 In addition, OTPs only exist in 20% of US counties,⁶³ and they are associated with additional stigma and barriers to optimal treatment of OUD.^36,64,65

Three important barriers related to methadone are worth noting. First, the standard starting dose (30–40 mg daily) for a new patient is much lower than the typical therapeutic dose range, regardless of the intensity of the patient’s opioid use. The dose escalation schedule is slow. Patients with heavy opioid use usually resort to illicit opioids until their methadone dose is therapeutic, which can take weeks to months.^35,66–69 Second, the restrictive take-home policies disrupt individuals’ daily lives and further propagate stigma and systematic cruelty, negatively affecting retention in care.³⁶ Third, establishing care at an OTP is challenging. Many OTPs operate at nearly full capacity and do not offer timely intake appointments. Intake appointments are usually scheduled early in the morning. The intake process is long and cumbersome, and patients may not even receive methadone on the same day.

Barriers to SSP

The implementation and expansion of SSP in the US have been challenging. Historically, federal regulations prohibited funding to SSP, and the “war on drugs” ideology and “not in my backyard” mentality further contributed to stigma.^70,71 After the 2015 HIV outbreak in Scott County, Indiana,⁷² regulations were relaxed to allow federal funds to support SSP operations, especially in vulnerable jurisdictions.⁷³ However, the purchase of syringes and needles with federal funds is still prohibited.^15,74 Many states have since authorized the operation of SSP, but legal restrictions and funding shortages remain. There may also be additional and contradictory policies from states and local jurisdictions about the operation of SSP.^75–77 Mail-order syringes⁷⁸ and prescribing syringes from primary care offices⁷⁷ may be worthy options to improve access to syringes. Careful navigation of legal barriers will be necessary to implement these programs.

Of particular concern, many SSPs provide one-for-one syringe exchange and impose a limit on the number of syringes exchanged per day. These practices are not consistent with the best practice of need-based exchange,⁷⁹ where PWID are given as many syringes as they request. For individuals who inject frequently, one-for-one exchange and a cap on exchange limit the ability to practice safe injections, thereby increasing the risk of infectious complications.

Substances used in the current wave of epidemic add challenges to addiction care and harm reduction

Illicitly manufactured fentanyl (IMF) and stimulants^80,81 account for the current wave of the substance use epidemic, and they render harm reduction practice and addiction care even more challenging.

The high potency and short duration of action of IMF make it more addictive and lead to more frequent injections. Increased injection frequency may have contributed to recent HIV outbreaks where SSP operations were robust.^82–85 The lipophilic property of IMF results in an adipose tissue reservoir that continues releasing IMF after cessation of use. This is thought to be the basis of unpredictable precipitated withdrawal related to buprenorphine,^86,87 a barrier to stabilization of addiction for PWID who use IMF.

PWID who inject stimulants face different challenges. The vasoconstrictive and analgesic effects of stimulants contribute to injection site injuries and increase the risk of infections.^88,89 Cocaine injection may be associated with periodic and high-frequency injection binges, leading to a higher risk of infections.⁹⁰ Furthermore, concurrent opioid and stimulant injection is shown to be related to higher injection frequency, higher perceived stigma, and unmet need for services.^91,92 Most SSPs are more familiar with services for PWID with OUD.⁸⁹ Therefore, PWID who inject stimulants may not utilize SSPs due to perceived lack of inclusion. To add complexity, no highly effective pharmacological treatment exists for stimulant use disorder. The first-line treatment is contingency management,⁹³ a conditioned, incentivizing behavior therapy. Its efficacy may be limited by availability and sustainability.

Barriers to oral PrEP for PWID

There is little research about the oral PrEP care cascade in PWID.^4,7,94,95 A multilevel model of barriers to PrEP for PWID included the following factors:^4,6,7,96 individual (e.g. unawareness of PrEP, lack of knowledge, low perceived HIV risk, competing priorities, concern about side effects and drug interactions, mistrust in healthcare, motivation), interpersonal (e.g. HIV stigma from partner, attitude of the social network), healthcare/clinical (e.g. provider literacy around PrEP, complex PrEP protocols, provider stigma, and provider willingness to prescribe PrEP), and structural (e.g. transportation, housing insecurity, and centralized PrEP prescription).

Most oral PrEP studies in PWID studied PrEP awareness, knowledge, risk perception, and willingness^4,7,97–105 and PrEP adherence.^{100,103–110} Notably, lack of community discussion, stigma against HIV, single-use injection, lack of sexual activity, and heterosexual behavior were related to low perceived risk for HIV in a qualitative study.¹¹¹ One study presented possible PrEP program scenarios, which included PrEP modalities and showed PWID favor long-acting (LA) oral PrEP¹¹² over LA injection or LA implantable PrEP.¹¹³ Very few studies examined factors that may affect clinicians’ decision-making, clinicians’ adoption and adherence to PrEP guidelines, or healthcare system delivery.^{94,99,104,105,107,108,114}

Strategies proposed to address barriers to the PrEP care cascade include those on the individual level (such as education, risk-based discussions, problem-solving, motivational interviewing, and incentivized adherence¹⁰⁷), the interpersonal level (such as peer- or social network-based interventions), the healthcare/clinical level (such as low-barrier care,¹¹⁵ same-day PrEP start,¹¹⁵ provider education such as “PrEP champions”,¹¹⁶ and culturally sensitive PrEP nurses and navigators), and the structural level (such as utilizing SSPs,^114,117 OTPs,¹¹⁸ other substance treatment facilities, community pharmacies,¹¹⁵ and mobile units).^7,95,119

Barriers to LA-PrEP for PWID

LA-PrEP (cabotegravir¹²⁰ and lenacapavir¹²¹) or other PrEP formulations (e.g. implants or vaginal rings¹²²) may help overcome some barriers to HIV prevention, but many challenges remain. We still need to mitigate upstream barriers such as poverty, food and housing insecurity, and health disparities.¹²³ One study found that barriers to LA-PrEP were cost, insurance, and implementation logistics.¹²⁴ Implementing LA-PrEP programs for PWID will likely need to build upon existing HIV/PrEP care delivery programs.^120,125 These programs will be resource intensive. It may not be easily disseminated to non-specialized settings such as primary care and addiction care facilities.

There are still unanswered questions about using LA-PrEP in PWID. It may be challenging to monitor seroconversion in PWID who may not routinely keep appointments. Even in LA-PrEP trial settings, seroconversion on LA-PrEP was subtle, and the diagnoses of HIV infection were delayed.¹²⁶ Additionally, it is unclear whether there will be injection risk compensation,¹²⁷ defined as increased risk behavior with the use of PrEP. Sexual risk compensation was observed in men who have sex with men utilizing PrEP.^128,129 Because of access disparities to SSPs, it remains to be seen if high-risk injection behaviors will be associated with PrEP among PWID. Injection risk compensation may inadvertently worsen non-HIV addiction-infection syndemics.

Proposed integrated strategies for HIV prevention in PWID

HIV prevention for PWID requires consideration of PrEP, MOUDs, SSPs, and a complement of behavioral interventions. PrEP should be offered as one component of a concerted response, but not to replace other HIV prevention strategies or be used in isolation.^85,95 Notably, the barriers to harm reduction and addiction care overlap with barriers to PrEP in PWID, and strategies that address multiple cross-cutting barriers should be prioritized.

In the following sections, the author proposes strategies to approach HIV prevention in PWID: comprehensive HIV risk assessment for PWID aided by checklists, cross-education between ID and addiction specialties, and integrated clinical care models.

Comprehensive HIV risk assessment for PWID

One-fifth to one-third of PWID are eligible for PrEP.^130,131 The CDC recommends evaluating both injection and sexual risks for HIV in this population.¹³² However, it is not uncommon that patients are only asked about injection or sex risk. A comprehensive assessment of HIV risk is crucial to educating and engaging patients and to facilitating success in HIV prevention.

With respect to injection-related risks, clinicians should be familiar with injection equipment and harm reduction counseling^71,133–135 (Table 4). They should inquire about sharing equipment other than syringes, and if the sharing practice is receptive (receiving equipment) or distributive (giving equipment). PWID form injection partnerships for multiple reasons, which include emotional support and overdose prevention.¹³⁶ A deeper understanding of these relational contexts may help engage PWID in HIV prevention at the individual and population levels.

Table 4.

Safe injection practices—six moments of infection prevention.

Moments	Safe injection practices
Syringe/needle acquisition before injection	Use new syringe/needle for each injection; one syringe/needle for one person
Water or acid to dissolve substance	Use sterile water; use single-use sachet of citric or ascorbic acid (vitamin C); do not use lemon juice
Cooker to prepare substance	Use clean cooker; one cooker for one person
Filtering impurity	Use clean single-use cotton filter; one filter for one person
Prepare the skin	Handwashing; wipe the skin with an alcohol swab
Syringe/needle disposal after injection	Do not lick the needle; dispose in a sharp container

Source: This framework is adapted from Harvey et al.¹³⁵

Studies have shown the complexity of injection equipment sharing. Two studies showed that, contrary to the traditional thoughts that cis-women often receive syringes from cis-men due to submissive roles in relationships, the equipment-sharing practices between heterosexual partners were both receptive and distributive by both genders.^137,138 Other studies showed that the urban/suburban/rural geographical difference¹³⁹ and characteristics of the injection networks, such as size, incarceration history, and social norms, affect PWID’s injection-related risk behaviors.^140,141

With respect to sexual risks, it has been shown that many equipment-sharing partnerships are also sexual.^136,138,142 Data from the 2022 National HIV Behavioral Surveillance for PWID showed a high percentage of condomless sex in the previous 12 months. Among cis-men, 63% of vaginal insertive sex encounters, 22% of anal insertive sex encounters with cis-women, and 5% of anal insertive/receptive sex encounters with men were condomless. Among cis-women, 72% of vaginal and 25% of anal receptive sex encounters were condomless. Twenty-six percent of male and 31% of female PWID reported unprotected sex with an HIV-serodiscordant partner at their last sexual encounter. Twenty-three percent of male and 31% of female PWID reported exchanging sex for money or drugs.¹⁴³ Those with primary stimulant use may have different injection-sexual risk behaviors.¹⁴⁴

ID and SUD checklists for education and clinical care

Checklists embedded in medical record templates with ID screening and SUD care components can be an effective tool to care for PWID. They have been used in office¹³⁴ and transition-of-care settings.^145–147 They can be used by non-addiction, non-ID/PrEP clinicians or non-clinical staff. However, currently available checklists are itemized and mainly used as reminders.

It will be useful to modify the checklists to include sexual and injection risks to form a risk assessment tool. An earlier HIV risk assessment tool for PWID was developed with data from a cohort of older Black men in Baltimore during the heroin epidemic,¹⁴⁸ but it had poor agreement in assessing PrEP eligibility with the current CDC PrEP guidelines.¹³⁰ An updated risk assessment tool may improve HIV prevention in PWID and help inform related PEP/PrEP guidelines.

ID-addiction educational and clinical integration

Clinical and educational integration between ID and addiction specialties is necessary to address HIV prevention in PWID. There are many mutual learning opportunities.^54,55,149 For example, ID clinicians can learn addiction and harm reduction practices, and addiction clinicians can learn sexual risk counseling and PrEP-related knowledge. SUD care coordination and medication assistance resources can be modeled after the Ryan White care coordination programs and antiretroviral therapy (ART) or PrEP drug assistance programs, respectively.

Addiction clinicians can be trained to increase PrEP uptake in outpatient^116,150 and inpatient settings.¹⁵¹ In one study of hospitalized PWID, addiction clinicians were involved in 84% of the post-exposure prophylaxis (PEP) or PrEP discharge prescriptions. The percentage of PEP/PrEP initiation in these PWID was incredibly low (6%), but it was already significantly higher than the national average.¹⁵¹ The findings suggested that addiction clinicians can be impactful in HIV prevention. This is important because not all hospitalized PWID will receive consultations from ID clinicians. When they are seen by ID clinicians, PrEP may not be a priority compared to more active ID issues.

In addition, harm reduction counseling and addiction care should be core competencies for ID physicians. ID physicians should assume the responsibility of prescribing buprenorphine or navigating the prescription and care resources for PWID. They should have basic operational knowledge of OTPs, SSPs, and knowledge of available community resources for PWID.

We need to systemically improve crossing education between ID and addiction. As such, we should strongly consider expanding combined ID/addiction^152,153 fellowship and addiction-focused tracks in ID fellowship programs. Outside of graduate medical education, Project ECHO (Extension for Community Healthcare Outcomes), a case-based educational teleconference, can effectively educate clinicians with limited access to clinical expertise, such as PrEP^154,155 and SUD care.^156,157 SUD and PrEP/ID clinicians can join remotely from the same or different institutions, which adds to flexibility and feasibility.

Integrated care delivery models in traditional healthcare settings

In the inpatient setting, there are multiple potential interventions. First, we should capitalize on collocated pharmacy and laboratory services for buprenorphine and PrEP provision.^158,159 Medications can be filled and sent to the patient’s room in the hospital. Second, we should seize the opportunity when PWID are hospitalized to screen for HIV and address challenges associated with outpatient PrEP initiation: HIV window period, lab testing, and multiple visits.¹⁶⁰ Studies showed low rates of HIV screening among hospitalized PWID,^151,161,162 but HIV screening tests are frequently ordered but not done because of patient refusal, initial focus on controlling withdrawal, challenges in phlebotomy, or patient-directed discharge. It is important to examine and address the inpatient HIV screening workflow. Third, we should utilize checklists for post-discharge care transition,^145,146 with post-discharge appointments scheduled soon after discharge.

In the ambulatory setting, we should expand integrated addiction-ID low-barrier outpatient care models^{145,159,163–165} that offer flexible hours, walk-in appointments, same-day medications, and collocated laboratory/pharmacy services.¹⁵⁸ One study demonstrated an effective integrated team that cared for patients from the hospital, through care transition, and to outpatient offices.¹⁴⁶ Such a longitudinal and integrated care model should be strongly encouraged to care for PWID. In addition, we should advocate for care coordination resources for PWID. Unlike the Ryan White Act resources available to persons with HIV, there is no specific fund for care coordination for PWID. Institutional support or grant funding is often needed for PWID to utilize care coordination resources.⁵³

Community pharmacies,^115,158 substance use detoxification or rehabilitation programs,¹⁶⁶ SSPs,^{99,105,114,117,167,168} and OTPs¹¹⁸ are venues where PWID can receive buprenorphine and PrEP. We need to strengthen the partnerships with these entities to better provide comprehensive HIV prevention services. ID clinicians should provide these partners with training in PrEP knowledge and PrEP-related program operations. We need to advocate for funding for SSPs and OTPs to implement PrEP programs.^118,169

Finally, telemedicine may be a strategy to reach out to PWID for buprenorphine, harm reduction, and PrEP. A study providing buprenorphine, harm reduction services, and PrEP is ongoing,¹¹⁴ and limited evidence showed tele-PrEP may improve PrEP uptake in PWID.¹⁷⁰

Integrated care by mobile health clinics (MHCs)

MHCs are “one-stop shop” care models to increase access to care. They provide buprenorphine, oral PrEP, and infectious diseases screening and treatment for PWID. They often provide navigation from peers or case managers. Some MHCs incorporate innovative features that potentially further improve are delivery to PWID. These features include an attached mobile retail pharmacy to an MHC with the capability of telemedicine visits with the clinicians,¹¹⁹ MHCs in multiple states with basic in-person primary care capabilities,¹⁷¹ and MHCs specifically for justice-involved PWID upon release to the community.¹⁷²

Currently, no MHCs dispense methadone, and the ability to dispense methadone from MHCs may improve HIV prevention for PWID. Even with the intensive support in a clinical trial that provided integrated care with buprenorphine and PrEP or ART for PWID through MHCs,¹⁷¹ MHC intervention was not associated with increased buprenorphine uptake. The intervention was also not associated with significantly higher PrEP uptake (11/203 in the intervention arm vs 6/206 in the control arm).¹⁷³ Methadone dispensed from MHCs may be advantageous. Methadone does not precipitate opioid withdrawal and may be more effective as a full opioid agonist to control addiction. One may hypothesize that improved addiction care may be associated with better PWID’s uptake of PrEP provision from MHCs. Despite their rarity at this time, we should strongly consider mobile methadone clinics^174,175 with MHC functions for HIV prevention.

A case study of integrated care amidst an HIV outbreak

Aggressive comprehensive HIV prevention services and treatment-as-prevention¹⁷⁶ are important during an outbreak.^72,84,85 Experiences from a recent IDU-associated HIV outbreak offer insights into such endeavors.

A realistic PEP-to-PrEP approach for PWID during an HIV outbreak is important for HIV prevention. A team from a low-barrier SUD clinic started at-risk PWID on PEP for 28 days, even if they were beyond the CDC-recommended 72-hour window since last exposure.¹⁶⁰ The approach is different from the current CDC guidelines.¹⁴³ The window period exists for both HIV viral load and antigen/antibody tests. It would be unrealistic to wait for negative HIV test results to start PrEP for a PWID during an outbreak. Patients would have ongoing risk and may not return to be started on PrEP on a later date. Same-day start PrEP risks HIV virological failure and resistance because of undiagnosed acute HIV. The PEP regimen would be an effective treatment even if patients have early HIV infection. PEP was transitioned to PrEP upon completion of the 28-day PEP course for those who tested negative for HIV infection.^{116,150,160,177}

Additionally, the same team utilized same-day ART start, street directly observed PEP/PrEP, and linkage to addiction treatment to care for PWID during the outbreak.¹⁷⁷ HIV viral suppression was achieved in 74% of 117 newly diagnosed patients and 90% of 29 new patients who were managed by the street outreach team.¹⁷⁷ Of note, many PWID still declined PEP/PrEP while engaging in other aspects of the care.¹⁵⁰ More studies are needed to understand the reasons why they declined PEP/PrEP.

Conclusion

To reverse the upward trend of the HIV epidemic in PWID, a comprehensive approach utilizing addiction care, harm reduction practices, and PrEP is necessary. We need to fill ID clinicians’ knowledge gaps in addiction care and harm reduction counseling. The ability to prescribe buprenorphine or navigate addiction care and harm reduction resources should be core competencies for ID clinicians. We should evaluate HIV risk systemically through injection and sexual risks. We need to establish cross-training between ID and addiction communities. We should devise integrated HIV prevention programs geared at points of intervention identified in this review. We should advocate for policy changes and funding for SSPs and OTPs. LA-PrEP can be a useful HIV prevention tool for PWID if we can implement robust programs to support its roll-out. We still need to address upstream barriers for PWID, such as stigma and health disparities.

Footnotes

Acknowledgements

The author thanks Drs. Helen Koenig and Jessica Meisner for their editing of and comments on the manuscript.

Author’s note

This review was based on a presentation given by the author at the 2024 Annual Philadelphia PrEP Week.

Declarations

ORCID iD

Wei-Teng Yang

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Integrating harm reduction and addiction care in HIV prevention among persons who inject drugs in the United States—a narrative review

Abstract

Keywords

Background

Methods

Harm reduction principles

Non-ART HIV prevention strategies in PWID

MOUD as HIV prevention

Clinical pearls about MOUD

SSP as HIV prevention

Current challenges in preventing HIV in PWID

Barriers to MOUD

Barriers to SSP

Substances used in the current wave of epidemic add challenges to addiction care and harm reduction

Barriers to oral PrEP for PWID

Barriers to LA-PrEP for PWID

Proposed integrated strategies for HIV prevention in PWID

Comprehensive HIV risk assessment for PWID

ID and SUD checklists for education and clinical care

ID-addiction educational and clinical integration

Integrated care delivery models in traditional healthcare settings

Integrated care by mobile health clinics (MHCs)

A case study of integrated care amidst an HIV outbreak

Conclusion

Footnotes

Acknowledgements

Author’s note

Declarations

ORCID iD

References