“Worn out”: Coping strategies for managing antiretroviral treatment fatigue among urban people of color living with HIV who were recently disengaged from outpatient HIV care

Abstract

Antiretroviral-related treatment fatigue is inconsistently defined in the literature on barriers to ART adherence. Research suggests that treatment fatigue is a salient challenge for people struggling with antiretroviral therapy adherence, but little is known about how people living with HIV attempt to manage this fatigue. Twenty-seven semi-structured interviews were conducted with low-income people of color living with HIV in NYC that were currently, or recently, disengaged from HIV care. The findings from this exploratory study suggest that treatment fatigue was common and that participants devised personal strategies to overcome it. These strategies included using reminder programs, requesting weekly rather than monthly pill quantities, and taking “pill holidays”. The varied nature- and varying levels of effectiveness- of these strategies highlight the need for specific programming to provide tailored support. Future research should examine treatment fatigue as a specific subtype of adherence challenge, and aim to define pill fatigue clearly.

Many people living with HIV (PLWH) face challenges to taking their HIV medication consistently. In the HIV care cascade, becoming linked to care, remaining engaged, and becoming fully antiretroviral therapy (ART) adherent is necessary to achieve viral suppression (Gardner, McLees, Steiner, Del Rio, & Burman, 2011; Mayer, Mugavero, Amico, Horn, & Thompson, 2013) and better quality of life (Airoldi et al., 2010; Claborn, Meier, Miller, & Leffingwell, 2015; Mannheimer et al., 2005; N. & F., 2014). Research has shown low income people of color in the U.S. struggle with ART adherence due to a variety of interrelated factors, including low health literacy (Fazeli, Woods, Gakumo, Mugavero, & Vance, 2019; R. J. Jacobs, Caballero, Ownby, Acevedo, & Kane, 2015; Simoni et al., 2012), housing instability, food insecurity (Palar et al., 2018; Surratt, O’Grady, Levi-Minzi, & Kurtz, 2015), transportation barriers (Cornelius et al., 2017), depression (Turan et al., 2017), substance use (Kalichman et al., 2015), and other psychosocial factors related to poverty and social exclusion (Kalichman & Grebler, 2010; Mimiaga et al., 2013). Yet, adherence challenges persist even when many of these factors are taken into consideration, which may suggest that other phenomena may be at play (Claborn et al., 2015).

While the ART adherence literature frequently mentions treatment fatigue (Claborn et al., 2015; Heckman, Mathew, & Carpenter, 2015; Mohd Salleh et al., 2018) as a potential barrier alongside side effects (Buehler & Spencer-Rodgers, 2017), there is a dearth of empirical data that specifically focuses on constitutes pill fatigue, and how the phenomenon both overlaps with and differs from other challenges to ART adherence, such as those related to side effects. In many cases, pill fatigue is noted, but not operationalized (Krummenacher, Cavassini, Bugnon, & Schneider, 2011; Mannheimer et al., 2005). In a recent systematic review of ART-related treatment fatigue, Claborn and colleagues note that the best available definition of the concept is provided by Miramontes (Miramontes, 2001), who characterizes treatment fatigue according to patient characteristics, such as life stressors and cultural beliefs; the patient-provider relationship, such as respect, trust and communication; and regimen issues, such as dosing restrictions and impact on lifestyle. Various terminology and characterizations are used to define HIV medication fatigue in the literature, but the studies included in the review did not provide a definition of pill fatigue, which suggests that while the phenomenon may be common, there is a lack of precision around the term (Simoni et al., 2012).

Notably, people living with other chronic diseases (e.g., diabetes, cancer, high blood pressure, etc.) that require routinized oral medication to achieve optimum treatment outcomes are also at risk of treatment fatigue, pill fatigue, and pill burden(J. M. Jacobs et al., 2019). Pill burden tends to relate to the quantity of pills needed to treat a condition or the impact that multiple-tablet regimen (MTR) use versus single-tablet regimen (STR) has on treatment adherence (Altice, Evuarherhe, Shina, Carter, & Beaubrun, 2019; N. & F., 2014). Claborn et al. proposes the use of the term “treatment regimen fatigue” to take into account the psychological fatigue dimensions associated with long-term HIV treatment. The data presented here support the notion of treatment fatigue, and we also posit that pill fatigue is a distinct characteristic of treatment fatigue that may overlap with, but also differ, from pill burden. This may especially be the case since newer classes of ART have significantly reduced pill burden. Thus, we define pill/treatment fatigue as feeling “worn out” by having to take ART every day, as well as the resulting behaviors, including medication forgetfulness, avoidant coping (taking “pill holidays”), and other strategies to manage, or overcome, this mental and physical fatigue.

Overall, the limited literature on ART-related pill fatigue coping strategies suggest that further exploration of this phenomenon is needed given its’ salience in the lives of many PLWH. More research is needed to better understand the specific mechanisms in which PLWH may experience and manage ART adherence when challenged with pill fatigue. The purpose of this analysis is to examine the various personal strategies used to attempt to manage pill fatigue among a sample of low-income, Black and Latinx people living with HIV who at the time of their interviews were in the preparation stage of medication reuptake, or had successfully resumed an ART regimen, after a period of relapse. In particular, the varied nature- and varying levels of effectiveness- of these strategies highlight the need for structured, formal programming to address treatment fatigue so people do not have to devise potentially ineffective strategies on their own.

Methods

Sample Study Population and Recruitment

From July 2015 to May 2016, 27 in-depth interviews were conducted with low-income Black and Latinx PLWH living in New York City. The study described here utilized a convenience sample from a larger NIH-funded investigation on disengagement from outpatient HIV care (referred to here as the parent study). The parent study recruited individuals who were hospitalized overnight or longer at the university hospital for unmanaged HIV. The study presented here followed up with a subset of individuals in order to explore participants’ ongoing challenges with re-engaging in care and/or re-starting an ART regimen after their initial parent interview. Given the difficulty of locating participants after their hospital discharge, the length of time between parent interview and follow up interview ranged from six months to two years.

The parent study assessed disengagement from HIV care in several ways using multiple criteria based on the literature and clinical gold standards (Mugavero et al 2010, Mugavero et al 2012). These following assessed engagement in HIV care: 1) CD4 cell count under 350; 2) if the individual had been seen by an outpatient HIV care provider in the past six months; 3) if the individual missed even one scheduled outpatient HIV care appointment; 4) if the individual was taking ART at the time of study enrollment, and 5) if the individual had attended two or more scheduled HIV care appointments in the past 12 months, and if so, were these scheduled visits separated by at least three months. At the time of the study presented here, all participants had been disengaged from outpatient HIV care within the previous six months to two years. Some had recently re-engaged in care, and many were still currently disengaged from outpatient HIV care but were trying to re-engage.

Locating potential participants was challenging due to their minimal engagement with the healthcare system related to housing instability, substance use, structural stigma and poverty. Several HIPAA-compliant strategies were used to locate potential participants, including contacting family and friends using information provided in the parent study, connecting with social workers and case managers, and working with the parent study’s patient coordinator to monitor new in-patient admissions. Overall, 33 individuals were successfully contacted, and a total of 27 participants were interviewed. Two individuals declined participation, citing lack of time. One individual agreed to participate but was not found to be mentally competent and was thus unable to provide informed consent. The remaining three individuals were initially reached via telephone, but their telephone numbers appeared to go out of service before an interview could be scheduled. The XXX Institutional Review Board approved this study, and all participants provided written consent.

Data Collection

Semi-structured interviews can generate novel insights by enabling participants to articulate their perspectives and life experiences in their own words (Patton 2005). A semi-structured interview guide was developed to explore challenges related to engagement in outpatient HIV care and adherence to HIV medication. Questions focused on participants’ experiences with their periods of disengagement and non-adherence, and their efforts to manage their HIV. It is important to note that the findings presented here, which are representative of the sample, were unanticipated and emerged from the data concerning participants’ experiences with ART adherence. Moreover, the researchers did not introduce the term “pill fatigue” to participants; rather, many participants used this language to describe their struggles with consistent adherence. Semi-structured interviews ranged from 25 minutes to two hours, with an average of approximately 45 minutes. Finally, a five to eight-minute interviewer-administered questionnaire (IAQ) was also completed with participants prior to the beginning of the qualitative portion to socio-demographic information. The first author, a trained qualitative interviewer, conducted the interviews. Differences in interpretation were resolved as a team in order to establish credibility, dependability, and confirmability of the findings.

Data Analysis

All interviews were audio recorded for professional transcription; twenty percent of transcriptions were checked for quality control. Participants were assigned pseudonyms to protect their confidentiality. Using a grounded theory approach to the dataset, the authors used multistep method to systematically identify and contextualize the themes present in the data, which included the development of a coding scheme and using it to discern patterns and subcategories. The analyses were closely reviewed by the research team to confirm the analyses and resolve any differences in interpretation. The software Atlas.ti was used to organize the qualitative data, and the socio-demographic data from the IAQ was generated using SPSS.

Results

Socio-demographic

The analytic sample consisted of 27 low-income PLWH of color. Table 1 describes the participant characteristics. Most of the participants were female (n = 16). The majority of participants were non-Hispanic Black (78%, n = 21), and 22% (n = 6) were Latinx. The age range of the sample was 28 to 55 years of age. All participants in the sample reported having Medicaid, and 93% reported that they lived in New York City-funded HIV/AIDS Services Administration housing or other public assistance-funded apartments, including single room occupancy housing (SRO).

Table 1.

Participant Socio-Demographics

Participants’ characteristics			n (%)
Age* [mean, SD]			[42.04, 8.11]
Gender	Female		16 (59%)
	Male		11 (41%)
Race & Ethnicity	Black Non-Hispanic		21 (78%)
	Hispanic / Latinx		6 (22%)
Current Housing Situation**	HASA or public assistance (apt or room)		18 (67%)
	SRO		7 (26%)
	No financial assistance		2 (7%)
	Nursing home or hospice		3 (11%)
	Homeless		8 (30%)
Health Insurance	Medicaid		25 (93%)
	Medicaid + Medicare		2 (7%)

Note:

^*Two participants did not report age

^**Adds up to >100% because some participants considered themselves homeless in addition to the housing category they selected (often a form of temporary housing). HASA = New York City-funded HIV/AIDS Services Administration; SRO = single room occupancy housing.

Strategies for managing pill fatigue

Pill fatigue was discussed by those currently adhering to their ART regimen, as well as by those contemplating to start or re-start ART in the near future. Many participants reported struggling with what they often termed “pill fatigue”, a phrase that appeared to describe being physically as well as emotionally worn out from having to take ART daily. In this sense, participants themselves informally defined pill fatigue in the context of their respective struggles with adherence. Although many also reported contending with side effects, participants seemed especially interested in discussing challenges unrelated to side effects, particularly pill fatigue, and the strategies they devised to overcome or manage this challenge. In this sense, pill fatigue appeared to intersect with participants other adherence-related challenges, suggesting that it may be one aspect interrelated with issues such as side effects, internalized stigma, and forgetfulness.

Maria, a 34-year old Latinx woman, was undetectable for the first time in her life, and was living in a nursing home at the time of the interview. She attributed her previous disengagement from HIV medical care to her alcohol use disorder. However, she had managed to become and stay sober since 2014, and this enabled her to manage her multiple health issues, including HIV and recently diagnosed narcolepsy. In the past, Maria had struggled with what she described as “pill fatigue,” but had enrolled in a cellphone/web-based adherence support program. This program required her to send a text message when she took her medication:

Interviewer: Do you think you’ll have—what will happen if you start encountering pill fatigue again or you don’t want take your HIV meds? How will you deal with that?

Maria: Well, I have an alarm set on my phone, so it constantly goes off if I don’t. I get annoyed…If I don’t type “okay” in a certain amount of time, it keeps going. It’s with a program called [name]…It’s been working good. Sometimes I take my medication, I forget to text “okay,” so I gotta go online and go to the website and let them know.

Luis, a 55-year old Latinx male, was diagnosed in 1988. At the time of the interview, he was preparing to leave his nursing facility of two years to move into an SRO until HASA could help him find an apartment. He had recently re-initiated ART, and was determined to take them consistently and avoid taking what he called “pill holidays”, i.e., periods of time when he would not take his medication. Luis’ experiences reveal the relationship between pill fatigue and his struggle with accepting his status. He explained that the motivation for taking a pill holiday was to feel normal and in control of his life, whereas when on medication, he felt he relinquished control of his life to the pills:

Interviewer: Since we saw you last, two years ago, have you had any of those feelings, that medication is just a negative reminder? [note: the participant had articulated that taking ART had been a constant “negative reminder” of his status in the parent study interview).

Luis: Sure, sure. To say no, I would be lying. Of course, I still get like that from time to time, that I say, damn. I have to take these pills for the rest of my life, and it’s a constant reminder…We have a thing—people that have the virus have a thing called—they take a [pill] vacation… Off for a couple of [meds], and I think I’m just gonna enjoy life. Just forget about everything. Just put everything down and try to be as normal as I can… I do that now and then, yeah. When I do it [take a pill holiday], I feel like I’m in more control of my life, man…I feel that I look at these pills and these things [are] controlling me…when I take the holiday and vacation, I feel in more control of my life. I’m not sick. I don’t have HIV for today. I don’t have no heart condition. I don’t have nothing.

To help avoid the temptation of taking a pill holiday, Luis also planned on asking his HIV provider for a pill tracker to assist him in remembering to take his ART:

As far as taking my [meds]—I’m gonna do everything in my power to keep up. I’m gonna get one of them—have a thing where they have—where it has days, and you got the pills in there… I’m gonna ask [my doctor what] to do—issue me one of those so I can put everything in that, yeah. Get me a watch with a timer, or on my phone. [Luis]

CeeCee, a 48 year old black woman diagnosed in 2006, had an undetectable viral load reported having been on ART consistently for one year at the time of her interview. She reported that it was previously difficult for her to stay consistently engaged in care because of alcohol and cocaine use, and mentioned that she had sometimes sold her HIV medication to pay for cocaine. She also experienced pill fatigue, which seemed to intersect with her issues with side effect-related nausea. When asked about her feelings about taking medication every day, CeeCee responded:

CeeCee: You do get tired…I say that every day.

Interviewer: What do you do [to overcome feeling tired]?

CeeCee: I just get over it. I say oh—I cry about it for a few minutes… I get my stomach ready. I just swallow. I just leave it there. Then, from thereon, I move on with my day.

Interviewer: How do you get your stomach ready?

CeeCee: I just say I know you’re gonna get nauseous a little bit. I just—I don’t even know how I really prepare it. I just say, “Come on. Let’s go. Get your water.” Then, I just gulp it. I don’t hold ‘em in my mouth long. I don’t procrastinate…Once I put ‘em in my hand, they gotta go down my throat. Cuz if I lay ‘em down somewhere, I might not take ‘em. I will have the forget syndrome and walk out the door.

Donna, a 33 year old Black woman diagnosed in 2008, planned to resume ART again after a period of inconsistent adherence due to pill fatigue. Being offered a one-pill-a-day option helped her feel able to commit to taking ART again. Although not all people living with HIV are a good match for the one-pill-a-day regimen, those who had switched to a simpler regimen reported that a single pill (versus multiple pills a day) helped them consistently take their medication. Donna explained:

Donna: My thing is I have a thing with a lot of pills. If it’s two pills, three maybe I can do it but when it’s like six, seven pills I’ll be like, “No, I don’t feel like taking it today.”…At that time I was on a lot of different pills. I’ll look at them, but I just won’t pick them up. …

Interviewer: What goes through your mind when you’re looking at all the bottles.

Interviewee: It’s like, “I’ll take them later.” [Donna]

Tina, a 53 year old Black woman quoted below, was diagnosed in 1995 and like many participants, had past struggles with pill fatigue, and forgetting to take her medication. She reported being adherent for a full year prior to the interview, and was on a two pill a day regimen. Having struggled with pill fatigue, and to avoid forgetting about the pills during the course of a busy or stressful day, she chose to not want to receive a full month of HIV medication at a time. Even though weekly pick up entailed traveling from Brooklyn to upper Manhattan, she preferred to obtain a less daunting quantity of pills that enabled her to feel capable of taking them daily:

…I’ll be doin’ so many other things that I’ll just lay there and just won’t take ‘em. I know what. That’s why I like to come pick ‘em up [in Manhattan, from Brooklyn] once a week ‘cause then—…Because if I have so many pills, I forget. If I got one case, I’ll keep lookin’ at that one case. If I got all them cases…sometimes I’m just not thinking about it. [Tina]

By devising strategies to overcome their respective challenges, it appeared that participants were able to feel more agentic and capable of consistently taking their medication. As all participants in the study had been recently disengaged from outpatient HIV care (with some of them having successfully re-started ART at the time of the interview), problem-solving strategies were necessary in order to achieve their goals of remaining adherent to their medication regimen despite these challenges. However, the effectiveness of these various strategies varied, and participants often expressed frustration, suggesting that social and clinical support is needed.

Discussion

Although the overarching purpose of the study was to broadly understand participants’ experiences with HIV care, the theme of treatment fatigue emerged as a salient aspect of people’s experience living with HIV. While not well-defined in the literature, ART-related treatment fatigue (or pill fatigue, which is the phrase some participants used to describe the complex combination of emotional and physical fatigue of taking HIV medication every day), is a phenomenon that patients experience and clinicians recognize. Importantly, participants’ diverse experiences contending with pill fatigue highlight the lack of coherent recommendations and programming around this phenomenon. The individualized nature of their respective strategies, and the varying degrees of success they had employing these strategies, suggests that ART fatigue is a common but under-addressed phenomenon.

Participants were both thoughtful and eager to reflect on their struggles with pill fatigue, and their devised strategies for overcoming it. Participants were often very aware of their respective tendencies that led to this manifestation of non-adherence, and discussed possible ways of addressing these tendencies that undermined their health and threatened their life. Participants’ respective strategies were varied, and some appeared to be more effective than others. While some reported using a phone alarm or apps to track adherence, or picking up weekly amounts of medication instead of a thirty day supply, other strategies, such as taking “pill holidays”, or as one participant put it, “cry[ing and getting over it]” seemed isolating and frustrating. These varied experiences contending with pill fatigue suggest that patients are often in the position of trying to devise strategies to overcome it without adequate clinical or social support.

Addressing ART fatigue specifically may be especially pertinent for PLWH who have been made socially and economically vulnerable. Although some people are candidates for one-pill-a-day options, and side effect profiles are lower than in the past (Truong et al 2015, Saag et al 2018), structural inequality makes it difficult for many PLWH to consistently adhere to their ART regimens. Indeed, participants’ daily lived experiences at the intersection of racism, classism and HIV stigma suggest that clinical and social support addressing ART fatigue may be especially beneficial (Jaiswal et al 2019). The critical role of social support in improving ART and other medication adherence is well-documented in the literature, and similar approaches could be used to address the unique challenges posed by ART fatigue (Scheurer et al 2012, Horvath et al 2013, Kelly et al 2014).

The implications for this research in clinical practice suggest several tactics. The first is to limit the clinical challenges of taking HIV medications by reducing pill burden and side effect profiles. Many PLWH have been on complex drug regimens involving taking multiple pills multiple times per day for years. Simplifying these, particularly to one-pill once daily regimens could dramatically reduce pill burden and possibly help reduce treatment fatigue. The second involves managing the medical side effects associated with taking ART medications, as side effects appeared to exacerbate pill fatigue. It is possible, for example, that an integrative health approach or dietary changes might assist with these side effects; for some populations, however, food insecurity concerns must be taken into account (Leyes, Martínez, & Forga, 2008; Weiser et al., 2011; Young, Wheeler, McCoy, & Weiser, 2014). However, decreasing pill burden and side effect profiles do not address the feelings of being “worn out”, but these strategies can help lessen the burdens often associated with treatment fatigue.

The more complex and internalized elements of illness and treatment fatigue, which may be driven by stigma of having HIV or more generally of being reminded of being “sick”, pose different challenges. Loneliness, isolation, and shame may play a role in these elements. Societally, reducing shame around HIV is crucial to eliminating treatment fatigue and denial around the need for adherence to ART medications (Earnshaw, Smith, Chaudoir, Amico, & Copenhaver, 2013; Katz et al., 2013). Addressing shame and isolation are especially pertinent, as the various coping strategies described by participants exist at the intersection of poverty and living with HIV. Unstable housing, mental health and substance use challenges also “wear out” participants, in addition to the burden of smaller tasks, such as refilling prescriptions and having frustrating or arduous interactions with the healthcare system. Thus, the role of social support in effectively addressing ART pill fatigue needs to be further elucidated in order to develop programming or interventions that are tailored for populations contending with multiple, interrelated structural barriers.

Future research must also take into account the varied ways in which people think about and experience treatment disruption. In the study presented here, the sample comprised people who were recently, or currently, disengaged from HIV care and/or had ART interruptions. Thus, most were still struggling with re-beginning ART, or consistently adhering and duration of ART varied widely and were often characterized by multiple periods of interruption. While some participants had been largely adherent for years before experiencing an interruption, most others reported that their treatment was affected due to a multitude of interrelated factors, such as housing instability, problematic substance use, stigma from loved ones and/or the healthcare system, and chronic poverty (Jaiswal et al 2020). Moreover, most participants had chronic comorbidities that also required ongoing medical care, and future research should also examine how ART fatigue may fit into a broader treatment fatigue related to polypharmacy. Finally, participants also described their adherence journeys in various ways, with different understandings of what it means to be adherent. Thus, researchers must consider how people’s daily lived experiences shape how they think about their adherence and their treatment goals.

Overall, the findings presented here underscore the importance of HIV care and social service providers recognizing pill fatigue among their patients, and working proactively to identify and implement potential strategies. In doing so, providers can help patients feel that they are not alone in trying to manage pill fatigue. Social workers and mental health providers in particular are uniquely positioned to address illness and treatment fatigue and advocate for the complex, psychosocial needs of their patients and clients.

Limitations

First, this research took place in New York City, where there is greater public health messaging and resources available to low-income PLWH as compared with many other parts of the country. Pill fatigue needs further exploration among other low-income PLWH who are living in less urban and potentially more underserved parts of the country with fewer available HIV-related resources. It is also important to note that while mention of pill fatigue emerged organically in the data, the interview guide was not initially designed to assess this phenomenon; further research is needed to more explicitly explore treatment and ART fatigue among low-income PLWH, particularly those that have struggled with remaining consistently engaged and adherent.

The study presented here offers a preliminary understanding of how treatment fatigue may be inextricably linked with other ART-related challenges, such as side effects, internalized feelings of shame, and forgetfulness. Beyond pill fatigue, participants appeared to be contending with a broader fatigue around their illness(es). In this sense, their ART-related fatigue was characterized by an emotional and physical tiredness of not only taking their pills every day, but also an exhaustion associated with being low income, HIV positive and dealing with various, interconnected challenges, including housing instability, substance use, mental health issues, stigma and discrimination. Thus, pill fatigue can co-exist with, and perhaps even perpetuate, other better-understood adherence barriers. Despite its relationship to other adherence challenges, future research should specifically explore pill fatigue as a potentially independent phenomenon, as well as a factor that can amplify or exacerbate other challenges to successfully managing their HIV. In particular, defining pill fatigue more concretely will serve to inform clinicians and social service providers as well as contribute to the development of effective interventions to address this manifestation of non-adherence.