The Challenges in Managing HIV in People Who Use Drugs

Abstract

Purpose of review

HIV management in PWUD is typically complex and challenging due to the presence of multiple medical and psychiatric comorbidities as well as social, physical, economic and legal factors that often disrupt the HIV continuum of care. In this review we describe the individual, health systems and societal barriers to HIV treatment access and care retention for people who use drugs. Additionally the clinical management of HIV infected PWUD is often complicated by the presence of multiple infectious and non-infectious comorbidities.

Recent findings

Improved ART adherence can be achieved through the provision of opiate substitution therapy (OST), directly administered antiretroviral therapy (DAART) and integration of ART with OST services. Recent advances with direct-acting antivirals (DAA) for HCV have shown superior outcomes compared to interferon based regimes in HIV-HCV co-infected patients. Newer diagnostic technologies for tuberculosis hold promise for earlier diagnosis for PWUD co-infected with TB

Summary

HIV-infected PWUDs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A comprehensive strategy that encompasses evidence-based prevention and treatment interventions that target the individual, family, healthcare system, legal and societal structure is required to ensure greater participation and success in HIV treatment and care.

Introduction

Although globally HIV incidence has decreased, low coverage of harm reduction and treatment services for people who use drugs (PWUD) has resulted in increases up to 30% for new HIV infections reported outside of Sub-Saharan Africa, particularly in Eastern Europe, Central Asia, the Middle East, North Africa and parts of South and East Asia.^1–3

Despite the volatile HIV epidemic among PWUD, especially in these low and middle-income countries (LMICs), the benefits from antiretroviral therapy (ART) in reducing HIV-related morbidity and mortality have been less pronounced among HIV-infected PWUD for several reasons.⁴ Indeed, mortality among PWUDs or alcohol is higher than their counterparts, even after controlling for ART access.⁵ First and foremost, HIV management in PWUD is typically complex and challenging due to the presence of multiple medical and psychiatric comorbidities⁶ as well as social, physical, economic and legal factors that often disrupt the HIV continuum of care, including delayed HIV diagnosis and entry into care, decreased ART access and adherence and poor long term retention in care. ^7–11 Approximately half of HIV-infected PWUDs have underlying mental illness, and both untreated mental illness or active drug use potentiates the risk of drug overdoses, violence and incarceration.^12–15 Shared transmission factors increase likelihood of HIV-infected PWUD becoming co-infected with viral hepatitis (HBV and HCV) and co-infection with tuberculosis facilitates disease progression, overlapping drug toxicities, drug-drug interactions and side-effects.⁶ Consequence, despite recent ART scale-up that now reaches 13 million people living with HIV (PLH) in LMICs, PWUD (~10% only) are disproportionately less likely than other PLH to receive ART^1,16,17 according to a World Bank analysis.¹⁸ Viewed across the HIV treatment cascade paradigm, HIV-infected PWUD face significant family and social, health-care system and individual level barriers to each step.^7,19,20 Achieving parity in prevention and treatment for PWUDs remains a challenge for individuals, healthcare systems and policy-makers alike. Overcoming obstacles along the entire HIV continuum of care (Figure 1) for PWUDs, from HIV testing through achieving viral suppression, is central to HIV treatment and prevention efforts.

Fig 1.

The HIV Continuum of Care for People Who Use Drugs: Strategies to Overcome Obstacles to Effective Treatment as Prevention

PLWH: people living with HIV; ART: antiretroviral therapy; NSEP: needle and syringe exchange programs; OST: opioid substitution therapy; DAART: directly administered antiretroviral therapy.

Challenges with HIV Diagnosis: The First Step Toward Treatment

In a recent review of access to HIV counselling and testing (HTC) in five countries in Central Asia where 60% of HIV infections are attributed to drug injection, the number of PWID who had been tested for HIV in the previous 12 months varied from 29% in Uzbekistan to 65% in Kazakhstan.²¹ In these countries and elsewhere, stigma, discrimination, human rights violations, and repressive legislation were found to be significant barriers to HTC in the countries examined.^22,23 Once diagnosed, PWUDs must be linked to HIV care. Numerous studies in high and LMICs have identified a number of issues related to linking PWUDs’ care. In one U.S. study, PWIDs had delays in linkage to care that exceeded 19 months.²⁴

Strategies to increase HIV testing such as on-site rapid HIV testing in drug treatment programs^25,26 and community based point-of-care testing through NSEPs and mobile medical units have been shown to increase the likelihood of HIV testing and successfully reached those who would not otherwise have been tested.^27,28 Recent data also support the use of peer-delivered strategies to increase HIV testing, which may further improve HIV testing rates for PWUDs.²⁹

Challenges in Treatment Access and Care Retention

Following HIV diagnosis, linkage and retention in care followed by ART initiation present extraordinary challenges for HIV-infected PWUD. Mutual lack of trust and suspicion between providers and PWUD delays entry into care, the first step of engagement, a scenario that has not improved much despite decades of experience in both high or LMICs.^7,20,30,31

A longitudinal assessment of HIV-infected PWIDs showed no substantial improvement in ART initiation over 12 years despite simplified and better-tolerated ART regimens and availability.³¹ Furthermore, compared to MSM in a Spanish cohort of PLH where over half of the participants were PWUD, PWUD were 33% less likely to initiate low ART; authors cited health professional’s fear of sub-optimal adherence and their inexperience with PWUDs as key contributors to late ART initiation³² despite evidence that PWUDs adhere to ART similarly to other PLH if provided adequate adherence support.³³ Both North American³⁴ and Malaysian³⁵ HIV specialists were significantly more likely to withhold ART from HIV-infected PWUDs unless they were abstinent from drugs, further contributing to treatment disparities. Clinicians cite ART non-adherence and development of antiretroviral resistance as major concerns,^34,36,37 despite a meta-analysis demonstrating that antiretroviral resistance among PWIDs and non-PWIDs did not differ.³⁸

Physicians often view drug users as manipulative, unmotivated, and undeserving of care while PWUD are often mistrustful of the health care system.^39–41 Healthcare avoidance by drug users is further exacerbated in countries where drug use is criminalized or compulsory detention for drug use is used as a means of “drug treatment”.^{17,42,43, 44}, 

With improved tolerability and convenience using contemporary ART regimens, evidence from both high⁴⁵ and LMIC⁴⁶ confirm improved short-term adherence among PWUD; from 1996 to 2009, >95% adherence increased from 19.3% to 65.9% in Canada.⁴⁷ Longer studies, however, suggest that a substantial proportion of PWUD either discontinue treatment or have sub-optimal adherence.^4,48–53,54 In the ALIVE cohort, for example, two-thirds of PWIDs were not retained in long-term with lack of healthcare insurance and suboptimal provider constancy contributing to reduced care retention, and active drug use further contributed to virological failure.⁵⁵

Interventions that improve ART adherence and viral suppression have been reviewed extensively.⁵⁶ Three interventions are recommended to improve viral suppression among HIV-infected PWUDs, including directly administered ART (DAART), providing opioid substitution therapy (OST) like methadone or buprenorphine to opioid dependent patients and integrating HIV and addiction services.⁵⁷ The best evidence to improve ART adherence is using DAART,^58–61 yet one recent study of stably methadone-maintained patients did not confirm this benefit.⁶² While DAART may involve increased human resources and be logistically challenging, a cost-effectiveness study integrating DAART into MMT support its use, especially in LMIC settings.⁶³ Considerable evidence for OST with buprenorphrine or methadone for opioid dependent patients exists to improve retention in care, ART uptake, ART adherence, and viral suppresion.^56,64–68 HIV-infected PWUDs who are in drug treatment adhere to ART similarly to non-PWUDs.^69,70 OST, including in LMICs,^71,72 improves HIV-related quality-of-life in HIV-infected PWUDs.⁷³ In studies of integrating buprenorphine into HIV care, retention in care⁷⁴ as well as improved ART initiation and viral suppression have been achieved.⁶⁴ Contingency management, and multi-component, nurse-delivered interventions have also significantly improved short-term adherence and virologic outcomes, but these effects were not sustained after intervention cessation.⁵⁶

Challenges in Clinical Management

The frequent co-occurrence of other infectious and non-infectious conditions in HIV-infected PWUD adds to the complexities in their clinical management.⁶ HIV/HCV co-infected persons have a 6-fold risk of end-stage liver disease and a 2-fold risk of cirrhosis compared with HCV mono-infected patients, leading to a 15%–25% prevalence of cirrhosis within 10–15 years of infection.^6,75,76 ART significantly reduces likelihood of hepatic decompensation in HIV/HCV-infected patients by 28%–41%.⁷⁷ HIV/HCV-infected patients are also at increased risk for cerobrovascular disease^78,79 and all-cause mortality^80,81 compared to HIV mono-infected patients, thus urging the need for expanded treatment.

HCV treatment in HIV/HCV co-infected patients presents unique challenges, including concerns about adherence, increased adverse side effects, and risk of reinfection from continued injection;⁸² as a result active drug users are unlikely to be treated⁸² and are excluded from clinical trials.⁸³ Before direct-acting antivirals (DAA) for HCV, lower sustained virological response (SVR) rates, longer treatment duration and more severe side effects reduced enthusiasm for pegylated interferon-based regimens in HIV/HCV co-infected patients.⁸⁴ First-generation DAAs like telaprevir and boceprevir, as well as newer DAAs like sofosbuvir and simeprevir markedly improved treatment responses over interferon-based regimens, however, pharmacological drug interactions and overlapping drug toxicities persist.^85,86

Interferon-free DAA regimens using sofosbuvir plus ribavirin show greater promise with SVRs in 84%–89% of HIV/HCV coinfected patients with genotypes 1–4,⁸⁷ while newer interferon-free regimens of ABT-450/ritonavir/ombitasvir/dasabuvir (ABT-333) with ribavirin for 12 weeks show SVRs of 94% in HIV/HCV patients with genotype 1.⁸⁸ Drug interactions and prohibitive costs of these new breakthroughs treatments, however, will restrict access to treatment for HIV PWUDs, especially in LMICs with limited resources and restricted ART options.^{89, 90} In the case of HIV/HBV coinfection, the combination of tenofovir with either lamivudine or emtricitabine is now universally recommended as integral to ART regimens to avoid selection and transmission of lamivudine-resistant HBV.⁹¹

Drug use, poverty, homelessness, overcrowding and imprisonment independently predispose PWUD to increased TB risk.^92–94 HIV-infected PWIDs have a 2–6-fold increased risk of developing TB compared with their non-using counterparts.^95,96 Challenges in managing HIV/TB co-infected PWUD are considerable, including delayed diagnosis, medication non-adherence and default from treatment and prophylaxis regimens, drug-drug interactions and increased hepatotoxicity risk.^92–94 Recent TB diagnostics developments, including point-of-care testing with Xpert® MTB/RIF and lipopolysaccharide antigen lipoarabinomannan (LAM) antigen urine testing, reduce repeated clinic attendance and accelerate treatment and potentially minimize treatment default among PWUD.^97–100 OST improves TB screening rates in HIV-infected PWIDs, receipt of preventive therapy and treatment adherence and persistence.^{6,72,101–103} TB treatment in HIV-infected PWUD is complicated by complex drug interactions and toxicites between medications to treat TB, HIV, and addiction.⁶ When OST, HIV and TB treatment are integrated in Ukraine, a recent study documented improved outcomes for each condition⁷² as well as improved adherence and retention in TB treatment for patients with TB disease.¹⁰¹

Poor hygiene, injection of nonsterile preparations, and poor technique predispose HIV-infected drug users to infections ranging from localised skin and soft-tissue infections to deep-seated infections including pyomyositis, septic arthritis, osteomyelitis, and endocarditis which may account for up to 25% of mortality in HIV-infected PWUD. Additionally, fatal outbreaks of botulism, tetanus, and fungal infections caused by injection of contaminated heroin have also been reported.⁶

Alcohol-use disorders and smoking are common in HIV infected PWUD. Heavy alcohol use contributes to the decreased retention in care and poor adherence to treatment as well as accelerate hepatic fibrosis in patients co-infected HCV. Similarly, the effects of smoking in HIV-infected drug users are often compounded by the added contribution of HCV, and some classes of ART that lead to accelerated atherosclerosis and increased morbidity and mortality.⁶

The prevalence of psychiatric disorders is high among HIV-infected PWUDs,^6,104 which further complicates management. Psychiatric disorders among HIV-infected PWUDs are associated with increased HIV behaviors, and suboptimal HIV outcomes in all aspects of the treatment cascade.¹⁰⁵ Central to improving HIV treatment outcomes is routine screening and pharmacological treatment,^57,106 which is fraught with some drug-drug interactions with OST.¹⁰⁷

Stigma and Discrimination

HIV-infected PWUDs often operate under the multiple veils of stigma from HIV, addiction, mental illness and criminal justice system involvement,¹⁰⁸ which often leads to discrimination. HIV-infected PWUDs and their families are isolated, despised and refused assistance by community members because they assume that those persons are unworthy. Stigma and discrimination often result in negative consequences like imposing shame, lack of trust or disowning them. Neighbors, employers and healthcare workers may similarly shame and discriminate against them, making the individual and family feel like outcasts and avoid treatment engagement.^109,110 Intransigent societal level stigma therefore impacts all aspects of the HIV treatment cascade and requires societal level interventions that protect HIV-infected PWUDs from discrimination.^111–113

Conclusion

HIV-infected PWUDs are a key population who in the absence of evidence-based prevention and treatment interventions that target the individual, family, healthcare system and societal structure, experience suboptimal outcomes along the HIV continuum of care. Scale-up of interventions and structural changes that improve their health, however, have the greatest benefit to improve society and reduce the scourges of the HIV pandemic.

Key points.

• The presence of multiple medical and psychiatric comorbidities as well as social, physical, economic and legal factors present a challenge in the HIV continuum of care for people who use drugs (PWUD)

• Long term adherence to ART has been shown to improve through interventions such as DAART, OST and integration of HIV treatment into substance abuse care

• Management of the HIV infected PWUD can be complex due to the presence of multiple infectious and noninfectious comorbidities. Earlier diagnosis of HIV and other infectious complications through improved testing technology and service delivery together with integration of service can improve treatment outcomes.