**1. Introduction**

Despite major progress in the effectiveness and availability of antiretroviral therapy (ART), considerable challenges in the treatment of people living with HIV (PLWH) remain. There are significant gaps in the HIV care continuum, with the greatest deficits seen in retaining individuals in care and achieving viral suppression. Of the 1.1 million individuals living with HIV in the U.S., the Centers for Disease Control and Prevention (CDC)

**Citation:** Traynor, S.M.; Schmidt, R.D.; Gooden, L.K.; Matheson, T.; Haynes, L.; Rodriguez, A.; Mugavero, M.; Jacobs, P.; Mandler, R.; Del Rio, C.; et al. Differential Effects of Patient Navigation across Latent Profiles of Barriers to Care among People Living with HIV and Comorbid Conditions. *J. Clin. Med.* **2023**, *12*, 114. https:// doi.org/10.3390/jcm12010114

Academic Editor: Icro Maremmani

Received: 2 November 2022 Revised: 29 November 2022 Accepted: 10 December 2022 Published: 23 December 2022

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

estimates that only 49% are continuously engaged or retained in HIV care and 53% have reached viral suppression [1]. One population that is particularly difficult to engage in care comprises people living with HIV who report substance use (PLWH-SU). In a 2018 review examining predictors of outcomes along the HIV care continuum, substance use was the most commonly cited risk factor associated with poor retention [2]. Compared to PLWH who report no substance use, those who use substances are less likely to access antiretroviral therapy, less likely to adhere to medication plans, and more likely to fall out of care [3]. Psychiatric comorbidities were also found to be predictors of poor retention in HIV care [4,5], and co-occurring diagnoses or "dual disorders"—the presence of both a substance use disorder and at least one psychiatric disorder [6]—among PLWH further complicate clinical managemen<sup>t</sup> and deter retention in treatment [7]. This can lead to uncontrolled infection, which contributes to ongoing disease transmission. The need for interventions to improve engagemen<sup>t</sup> of this high-risk population in HIV care remains a national public health priority [8].

To understand why PLWH-SU do not engage in care, it is necessary to recognize the challenges they face in accessing care. This requires a thorough examination of multi-level factors, including social determinants of health, associated with access to and retention in HIV care. Data from the 2016 sample of the Medical Monitoring Project, a nationally representative sample of all adults diagnosed with HIV in the U.S., showed that 42% of respondents had household incomes below the federal poverty threshold and 43% were unemployed [9]. These factors have consistently been shown to severely limit the resources available to obtain healthcare [10–12]. Additionally, 22% and 26% of respondents reported symptoms of depression and anxiety, respectively, both of which are associated with lowered healthcare utilization and poor adherence to treatment plans [9,13–15]. Other barriers to HIV treatment identified through both qualitative and quantitative studies include housing instability [11,16–19], food insecurity [16,20,21], transportation [18,22], substance use [2,23,24], intimate partner violence (IPV) [25,26], perceived stigma [23], discrimination [27], clinic location and hours [24], service availability [26], and privacy concerns [24,28]. Self-perceived barriers to care, including financial, structural, and logistical barriers, as well as concerns about personal health or service delivery, have been associated with higher rates of mortality among PLWH [29]. For PLWH-SU, their substance use presents additional barriers to care, such as stigma, incarceration, and difficulty maintaining scheduled treatment regimens [30–33].

One intervention specifically designed to help individuals overcome barriers to care is patient navigation (PN). PN is a patient-centered intervention that identifies strategies to eliminate barriers to care and guides individuals through the healthcare system. It employs a strengths-based case managemen<sup>t</sup> approach [34] and motivational interviewing [35] to empower individuals to manage their healthcare. Examples of activities involved in PN include helping individuals obtain health insurance, scheduling medical appointments, arranging transportation or childcare services, and providing assistance in applying for social services [36]. Screening for social determinants of health, such as housing, is another critical navigation activity [37]. PN may be combined with other tools such as contingency managemen<sup>t</sup> (CM), which offers financial incentives for completing various activities of a treatment plan. The use of incentives has been specifically useful for engaging people who use drugs and/or alcohol [38,39]. PN strategies can help individuals with layered and complex mental health and/or addictions overcome barriers to obtaining services from various, and often fragmented, systems [40,41].

Although PN was initially developed to help predominantly underrepresented minority women access breast cancer screening and treatment services, it is now used for a variety of patient populations [42,43]. Among PLWH, results of studies assessing the effect of PN on HIV care have been mixed. Some studies have shown that PN is efficacious for linking individuals to care and improving steps along the HIV care continuum [34,44–46], while others reported no effect [47,48]. These conflicting results have raised questions about the effectiveness of PN and warrant additional research to determine for which

populations and in what circumstances PN is most beneficial [49]. The effectiveness of PN has been difficult to establish, in part because PN is classified as a "complex intervention." This means that it consists of several core components, targets multiple behaviors, and is often tailored to meet specific conditions [50,51]. The many sources of variation make it difficult to determine which aspects of the intervention are most beneficial. In the case of PN, intervention activities are highly dependent on the specific barriers encountered by each individual. Therefore, it is possible that PN works better for certain patients than for others, depending on the type and number of barriers experienced.

It is also possible that the combination of healthcare barriers, stemming from social determinants of health and other individual and interpersonal factors, may influence the effectiveness of an intervention such as PN on HIV care. Because many PLWH face multiple, concurrent barriers, there is a growing number of studies supporting the use of a syndemics framework for describing factors that influence HIV infection. The syndemics approach suggests that there is an overlap of interrelated factors that drives risk for multiple, cooccurring conditions [52]. Previous studies have identified several syndemic conditions known to occur among PLWH; these include mental illness, violence, homelessness, and socioeconomic disadvantage [53,54]. Previous research has shown that PLWH have an average of two to four syndemic conditions, but some may experience as many as eight conditions [55]. Studies have also shown that these concomitant syndemic factors act synergistically to produce poor health outcomes. For example, research on the interplay among psychosocial factors, substance use, and HIV risk-taking suggests that psychological problems and substance use interact to not only negatively impact retention in care [2], but are also associated with increased risky behaviors [56]. The clustering of risk factors creates a syndemic vulnerability that places individuals at increased risk for HIV acquisition, high-risk sexual behaviors, sexually transmitted infections, and more frequent substance use [52,57].

Additional work has been done to examine syndemic vulnerability as it relates to the HIV care continuum. Glynn et al. (2019) found that among PLWH in Miami, Florida, the odds of having low ART adherence (<80%) and unsuppressed viral load increased for every syndemic condition experienced [55]. This finding supported previous work showing that a higher number of syndemic factors is associated with poor medication adherence and lower odds of viral suppression [58,59]. In 2015, Mizuno et al. (2015) examined syndemic factors specifically among persons who inject drugs and found similar results [57]. All outcomes along the HIV care continuum worsened as the number of psychosocial risk factors increased.

Despite the insights of this previous research, it is limited, in that syndemic barriers to care are measured as a sum of the number of syndemic factors an individual experiences. This composite-score approach places equal weight on the influence of each risk factor and suggests that simply minimizing the number of barriers can lead to improved outcomes. It is possible, however, that the pattern of factors an individual faces is more important than simply the number of barriers. Some syndemic factors may be more significant barriers to treatment than others. Some barriers may be more likely to cluster together than other barriers, creating subgroups of individuals characterized by different combinations of healthcare barriers. Thus, examining patterns of experienced barriers and the impact of these patterns on subsequent health outcomes may provide an improved understanding of how individuals respond to interventions designed to address healthcare barriers.

The current study has two main objectives. The first objective is to describe subgroups of PLWH-SU that share common patterns of barriers to care. The second objective is to analyze how subgroup membership influences the association between PN interventions and HIV outcomes. The data for this study come from CTN-0049, a randomized, controlled trial that studied PN in a sample of 801 hospitalized PLWH-SU who had uncontrolled HIV [60]. The trial tested the effect of a 6-month PN intervention, offered with and without CM, on engagemen<sup>t</sup> in care and viral suppression at 6 and 12 months. The results showed that the PN and PN+CM interventions were effective for engaging participants in care at 6 months, and PN+CM was effective for viral suppression at 6 months. Although these

effects were not maintained through the 12-month follow-up period, CTN-0049 provides a unique opportunity to explore factors that contributed to the short-term success of the intervention. The data from this study may help characterize the populations likely to benefit from PN; this characterization can inform future adjustments to the intervention, maximize its effectiveness, and result in a more efficient allocation of resources.

#### **2. Materials and Methods**

#### *2.1. CTN-0049 Overview*

The CTN-0049 study was a randomized, controlled trial supported by the National Institute on Drug Abuse's National Drug Abuse Treatment Clinical Trials Network and has been described in detail elsewhere [61]. Briefly, the purpose of CTN-0049 was to determine the effect of a structured PN intervention, delivered with or without CM, on HIV health outcomes among hospitalized PLWH-SU with advanced HIV disease. Participants were recruited between July 2012 and January 2014 from 11 U.S. hospitals with both a high HIV inpatient census and a high prevalence of substance use among patients. Patients were eligible for enrollment if they had a clinical indication that they were out of HIV care and had evidence of substance use in the past 12 months. A total of 801 participants were randomized to one of three treatment groups: (1) PN, (2) PN+CM, or (3) treatment as usual (TAU). Those randomized to one of the PN groups were offered up to 11 PN sessions over a 6-month intervention period. During sessions, navigators used a strengths-based case managemen<sup>t</sup> approach to assist patients to coordinate care with clinicians, review their health information, address personal challenges, and provide direct psychosocial support. Those in PN+CM also received financial incentives for target behaviors, including session attendance, completion of paperwork, HIV clinic visits, SUD treatment visits, negative substance use specimens, blood draws, and active ART prescriptions. Participants in the TAU group did not interact with the patient navigators, and received the standard treatment provided at their hospital for linking hospitalized patients to outpatient HIV care and substance-use-disorders treatment, which at most hospitals was written referral. Patients were followed up at 6 months (*n* = 761) and 12 months (*n* = 752) post-randomization and assessed for HIV viral load and other outcomes; however, no differences in rates of HIV viral suppression or death among the three groups at 12 months were revealed.
