Abstract
Background:
This mini-review examines the clinical significance of patient-reported outcomes (PROs) in the care of individuals living with HIV (PLWH), focusing on their potential to enhance patient-centered medicine, treatment adherence, and quality of life.
Methods:
The review explores various types of PROs, their applications, and implications for future HIV care practices. It discusses HIV-specific PROs, such as the HIV-Symptom index and HIV Treatment Satisfaction Questionnaire, along with general PROs assessing symptoms, treatment satisfaction, adherence, and health-related quality of life (HRQOL).
Results:
PLWH often experience lower HRQOL, influenced by HIV-related symptoms, comorbidities, and psychosocial factors. However, ART modifications and simplified treatment regimens show promise in improving HRQOL. PROs have been instrumental in evaluating the efficacy of therapeutic agents in clinical trials and real-world clinical practice. Incorporating PROs into routine clinical care can lead to better understanding of PLWH's conditions, improved medication adherence, and enhanced quality of care.
Conclusion:
As patient-centered care becomes increasingly important in HIV management, PROs are poised to play a crucial role in shaping the future of HIV treatment practices, facilitating better communication between healthcare providers and patients, and ultimately improving outcomes for PLWH.
Introduction
Since the discovery of human immunodeficiency virus (HIV) in 1981 and the development of zidovudine as a therapeutic agent in 1987, the treatment of HIV infection has focused on suppressing viral replication and restoring immune function.1,2 However, recent advancements in antiretroviral therapy (ART) have made viral suppression easily achievable, leading to extended survival of people living with HIV (PLWH).3–5 HIV infection is a chronic and medically manageable condition for most people who have access to ART.6 Conversely, the management of chronic comorbidities, such as atherosclerosis and chronic kidney disease, has emerged as a significant concern, contributing to a decline in health-related quality of life (QOL) in PLWH.7,8 Moreover, many other conditions associated with aging, such as cardiovascular disease, fatty liver disease, central nervous system disorders, fracture risk, and osteoporosis, are more common in PLWH than in the general population.9,10 Additionally, the presence of unique factors, including HIV-related stigma, further contributes to diminished QOL.11,12 In recent years, achieving and maintaining optimal health-related QOL has emerged as a key goal in treating PLWH, supplementing the ambitious treatment target of 90-90-90 by 2020 set by the Joint United Nations Program on HIV/acquired immunodeficiency syndrome (AIDS).13 Notably, many experts recognize the necessity of implementing patient-centered care to achieve this goal.14–16
One proposed solution for implementing patient-centered care, particularly in the context of HIV care, is the utilization of patient-reported outcomes (PROs) in standard medical practice. PROs are outcomes reported directly by patients and are often collected through questionnaires to assess the patient’s condition accurately. Oncology is an early adopter of PROs. Studies have revealed significant disparities between healthcare providers’ (HCPs’) perceptions of chemotherapy side effects and the actual experiences reported by patients with cancer, highlighting the effectiveness of PROs.17 Additionally, the use of PROs has been associated withimproved communication between HCPs and patients.18,19
With a view toward medical practice for HIV/AIDS, PROs are thought to be particularly valuable for understanding the conditions commonly experienced by PLWH, such as anxiety and depression, and for addressing the challenges posed by HIV-related stigma and prevalent comorbidities. In recent years, the usefulness of PROs has been gradually recognized in the field of HIV, and many studies have been conducted. In this review, we introduce some of these studies and discuss the position and prospects of PROs in future clinical practice for PLWH.
Types of PROs
PROs are of various types. First, there are several HIV-specific PROs.20,21 For example, the HIV-symptom index (SI) is a validated PRO instrument that assesses the burden of 20 common symptoms associated with HIV treatment or infection to better understand the status of PLWH.22 This instrument is considered one of the major measures in HIV clinical research related to patient symptoms. The HIV Treatment Satisfaction Questionnaire evaluates satisfaction with HIV care. HIV-specific PROs offer a more precise understanding of not only symptoms but also patients’ perspectives and conditions, which are challenging to assess in routine medical care.23 Furthermore, other scales include theHIV Disability Questionnaire, HIV Stigma Scale, Patient-Reported Outcome Quality Of Life-HIV (PROQOL-HIV), and Medical Outcomes Study HIV Health Survey (MOS-HIV).24–27 Specifically, PROQOL-HIV and MOS-HIV are measures of healthcare-related quality of life (HRQOL). Moreover, many other scales are widely used for patients with various conditions, regardless of the disease. For instance, the Pittsburgh Sleep Quality Index assesses sleep quality, enabling objective evaluation of sleep disorders.28 The Patient Health Questionnaire-9 is widely utilized to evaluate the state of depression.29 The Medication Adherence Reasons Scale is a 20-item, self-reported, comprehensive scale developed to measure two aspects of medication nonadherence: the extent or frequency of nonadherence and reasons for nonadherence.30 Importantly, these scales, including those related to the HIV infection, are often used in clinical research.
Next, in terms of purpose, PROs can be classified into three categories: those who assess subjective symptoms, those who reflect patients’ thoughts and opinions about medical treatment/care, such as satisfaction and adherence, and those who assess QOL. Among these, QOL evaluation is deemed highly indicative of PROs’ value. Assessing QOL is particularly challenging owing to its subjective nature. Capturing QOL is complex because of this subjectivity. However, certain PROs can effectively quantify QOL. Consequently, these tools are applicable in various clinical settings. For instance, MOS Short-Form 36-Item Health Survey (SF-36) and euroqol 5-dimension 3-level (EQ-5D-3L) are prominent QOL scales used in clinical practice.31,32 As mentioned previously, the PROQOL-HIV and MOS-HIV are the major QOL scales for PLWH.
PROs presented in this chapter are summarized in Table1. In practice, it is necessary to select some of these PROs in research, real-world clinical practice, etc. First, all of the PROs are highly useful for understanding the patient's background and condition because they are tools that pick up the patient's voice. Especially, PROs that assess QOL may provide a more accurate picture of a patient's condition. PROs that assess thoughts and opinions about treatment, such as treatment satisfaction, are better suited to evaluate changes in condition following interventions such as treatment, and are in fact used in many clinical studies. In order to improve the quality of actual medical care, PROs that assess symptoms and summarize thoughts and opinions about medical care and past experiences are considered more suitable because they can supply information about patient-related conditions and improve communication between HCPs and patients. In particular, PROs that assess symptoms have the potential to reveal diseases and conditions that are not recognized in usual medical care. In the chapters that follow, reports on PROs associated with HIV medicine that have been published are briefly summarized.
Summary of the representative patient reported outcomes described in the review
PROs and QOL in PLWH
Evidence indicates that PLWH often experience a lower QOL, with numerous studies focusing on QOL assessment in PLWH through the use of PROs. Indeed, one study highlighted that HIV infection alone can decrease QOL.33 Notably, high rates of mental QOL decline have been observed among PLWH.34–37 A recent report identified that HIV-associated neurocognitive disorder, a significant complication in PLWH, markedly reduces QOL.38 Another study showed a significant correlation between sexual satisfaction and HRQOL in PLWH.39 Various factors in PLWH, including symptoms of chronic obstructive pulmonary disease, pain associated with menopause, and leishmaniasis, have been documented to significantly impact on HRQOL.40,41 However, decreased QOL has been demonstrated to improve with the introduction of ART in naïve patients and with ART modification in treated patients due to adverse reactions to treatment.42 Recent treatment simplifications in patients have also been demonstrated to improve sleep quality and mental QOL.43 Notably, these reports indicate that poor QOL remains an important issue in HIV, and some types of HIV treatment regimens can affect the HRQOL of PLWH. Measurement of QOL using PRO in PLWH might be clinically valuable because it allows us to understand the situation of PLWH and decreases the gap between HCPs and PLWH.
PROs and ART
Owing to the significant advances in anti-HIV drugs, there has been little difference between recent therapies in suppressing viral replication and restoring immunocompetence. Therefore, other measures are required to determine the differences between treatments. Consequently, a variety of PROs are now being used in studies on therapeutic agent evaluation, including phase 3 randomized clinical trials.
For example, a single-tablet regimen was reported tobe more satisfactory for PLWH than a multitablet regimen.44 Regarding dolutegravir, one study that used PROs to assess the status of patients on dolutegravir-based therapy reported that more than half of the participants were satisfied with their treatment and had a good QOL.45 In a study of female PLWH, a change from tenofovir disoproxil fumarate/emtricitabine plus a non-nucleoside reverse transcriptase inhibitor to abacavir/lamivudine/dolutegravir, a single-tablet regimen, was reported to have no effect on anxiety, depression, or sleep, based on PROs.46 In contrast, we have reported that recent treatment simplifications significantly improve sleep quality and mental QOL.43 Additionally, a study on the real-world clinical efficacy of bictegravir indicated that changes in treatment medication enhanced some symptoms, as confirmed by HIV-SI, a type of PRO instrument.47 Numerous recent studies have utilized PROs to evaluate the efficacy of therapeutic agents. Notably, PROs have also been applied in clinical research during the phase 2b and phase 3 stages of drug development. For instance, in the First Long-Acting Injectable Regimen (FLAIR), phase 3 Antiretroviral Therapy as Long Acting Suppression (ATLAS), and Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M) clinical studies of cabotegravir/rilpivirine injectable drugs, PROs were employed to assess treatment satisfaction. These studies revealed high participant satisfaction with the novel injectable treatment.48–50 Moreover, PROs have been used in several clinical trials.51 Given the characteristics of PROs, their incorporation in studies for evaluating the efficacy of therapeutic agents in clinical practice and clinical trials of premarketing therapeutic agents represents an effective approach to identify the optimal treatment for patients.
Application of PROs to real-life clinical practice
Toward the practice of patient-centered medicine
Recently, numerous experts have recognized the importance of PROs in real-world clinical practice for HIV. A study found that PROs concerning depression, its risk factors, and feedback to HCPs improved the precise description of treatment adherence and increased the likelihood of follow-up for depression.52 This finding indicates that PROs can improve the quality of medical care. Similarly, a report suggests that PROs on drugs and mental health have changed HCPs’ care and behavior toward PLWH and have led to HCPs encouraging PLWH to participate in certain correctional programs.53 Another research showed a decreased in the number of suicide attempts and anxiety complaints after initiation of the use of some mental-associated PROs that were recorded at every visit and feedback provided to HCPs.54 The cross-sectional use of Ambuflex PRO, a set of questions about physical symptoms in clinical practice, has been reported to detect physical and cognitive problems that go unnoticed in usual care.55
These data indicate that the use of PROs allows HCPs to better understand the situation of PLWH, which may be the result of better communication between them. Additionally, several real-world studies have shown that even the use of temporary PROs in clinical studies can provide high-quality medical care, which improves QOL of PLWH. The findings advocate for the ongoing implementation of PROs in real-life clinical settings. Notably, experts have recently proposed that PRO questions should be selected with consideration for application in typical clinical practice. Additionally, the development of electronic PROs, accessible via tablets, aligns well with standard clinical procedures. Furthermore, the use of PROs in family medicine clinics, external to hospital environments, is also deemed appropriate for routine clinical practice.56–58
As a support for medical practice
PROs have the potential to enhance medication adherence. Several experts have endeavored to develop PROs to evaluate barriers to ART and have demonstrated their effectiveness in adherence.59–61 Specifically, a few reports have shown that the use of uniquely developed PROs may lead to better medical adherence in PLWH.62 Medical adherence is an issue in the management of medical practices in PLWH, and PROs may contribute to improving the quality of PLWH management in the future by improving medical adherence.
Another crucial aspect of PLWH management involves regular checkups, and certain reports indicate that PROs might predict the probability of errors during these checkups. Indeed, in particular tailored PROs that assess the status of PLWH or their adherence to care could foresee the likelihood of missing actual medical appointments.63,64 These factors may contribute to improving the quality of PLWH management.
Future of HIV treatment and PROs
In recent years, HCPs are increasingly mandated to practice patient-centered care for PLWH. PROs have demonstrated the potential to enhance care quality by offering diverse information on stigma, substance use, and adherence, aspects often not fully comprehended in standard practice. Indeed, several experts believe that PROs ought to be integrated into clinical practice as standard clinical tools.56,65 Recently, PROs have also been used in clinical studies. However, considering the results of these studies and the features of PROs, we should realize the potential of PROs in usual clinical practice for PLWH and prepare to use PROs in real-world clinical practice.