Palliative care considerations for the older adults with HIV/AIDS: a clinical practice review

Introduction

Palliative care is a specialized medical care approach that focuses on improving the quality of life for individuals facing serious, life-limiting illnesses. The primary goal of palliative care is to provide relief from the symptoms and stress associated with the illness, with the aim of enhancing the overall quality of life of the patient. Palliative care is comprehensive and addresses physical symptoms, emotional, social, and spiritual needs of patients. It is not limited to end-of-life care; rather, it can be integrated at any stage of a serious illness, alongside curative or life-prolonging treatments.

Palliative care is categorized into primary and specialist levels. Primary palliative care represents the foundational level, seamlessly integrated into the routine care administered by health professionals who are not palliative care specialists. It encompasses the management of common symptoms, provision of basic emotional and psychological support, and facilitation of discussions regarding prognosis and care objectives. Conversely, specialist palliative care is delivered by healthcare professionals with specialized training and expertise in this field. This advanced level of care is typically reserved for more complex or challenging cases, necessitating sophisticated symptom management, navigation of intricate family dynamics, or intricate decision-making processes concerning the illness trajectory. Teams providing specialist palliative care commonly comprise palliative care physicians, advanced practice nurses, physician assistants, social workers, chaplains, and other professionals such as music therapist, nutritionist, psychologist. Together, they offer comprehensive support to patients experiencing serious, life-limiting illnesses and their families.

Regular human immunodeficiency virus (HIV) testing and prompt initiation of antiretroviral therapy (ART) have significantly improved life expectancy in people living with HIV (PLWH) transforming HIV from a terminal diagnosis to a manageable condition (1,2). In 2021, over half of the HIV-positive population was aged 50 years or older, with this age group also accounting for 16% of new diagnoses, indicating an aging HIV-positive demographic. The proportion of PLWH who are 50 years and above is projected to continue to increase both in the US and globally. In fact, it is estimated that by 2030, 73% of PLWH will be older than 50 years (3). These individuals aging with HIV are disproportionately and prematurely impacted by conditions associated with aging, such as multimorbidity, cardiovascular disease polypharmacy, cognitive impairment, and functional decline (4).

The care of people aging with HIV is thus evolving from a narrow focus on HIV disease and its associated opportunistic infections (OIs), to complex care management of multiple chronic illnesses that requires a multidisciplinary approach. This review focuses on addressing the palliative care needs of older adults living with HIV and multiple chronic illnesses, and it also explores the existing gaps in the delivery of palliative care.

Methods

The online search held by using databases OVID Medline(R), PubMed, Cochrane Database of Systematic Reviews, Google Scholar, with search terms “HIV, AIDS, palliative care, end of life care, mortality, causes of mortality and advance care planning, hospice” to target current palliative care models, prognostication and screening tools. We aimed to find care gaps and provide recommendations on how to integrate palliative care to care of people aging with HIV. Total 1,184 publications found, and 211 were for full text reviewing. Total of 73 articles published in peer reviewed journals are included. The review of 26 peer reviewed articles published in USA was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) (5).

Understanding the impact of aging and HIV related co-morbidities

Older adults with HIV are now experiencing typical age-associated conditions such as cardiovascular disease, low bone density, and neurocognitive disorders; however, HIV and its treatment can also exacerbate these issues, leading to heightened vulnerability. Non-acquired immunodeficiency syndrome (non-AIDS) causes of mortality in the context of widespread ART can be broadly categorized into three main areas: comorbidities, lifestyle factors, and medication-related complications. This highlights the importance of early diagnosis, management of comorbidities, and age-appropriate screening (6).

Aside from the increased risk of non-HIV related comorbidities such as cardiovascular disease, diabetes, liver disease, and non-AIDS-associated malignancies, there is also increased risk for neuro-cognitive impairment and depression (7). These comorbidities can significantly impact the quality of life for older adults and increase the risk of mortality. Lifestyle factors, such as smoking, and substance use can contribute to non-AIDS causes of mortality in people living with HIV (8).

A new study analyzing data from 33,200 adults between the ages of 18 and 59 revealed that health disparities between individuals with and without HIV become more pronounced with age (9). These age-related differences are potentially attributable to later diagnoses in older patients, as well as less effective responses to ART, such as lower CD4 counts which might be associated with a mediated immune reconstitution (10).

The co-administration of antiretroviral drugs and other medications is frequently observed in older adults, making this demographic more susceptible to adverse events related to drug-drug interactions (11). Collaboration between health care providers and a pharmacist to identify and mitigate potential drug-drug interactions and negative side effects is essential for maintaining the health and wellness of people living with HIV who are also managing multiple coexisting conditions. Turrini et al. have reported that individuals with HIV are statistically more likely to have higher odds of depression, chronic kidney disease, chronic obstructive pulmonary disease (COPD), osteoporosis, hypertension, ischemic heart disease, diabetes, chronic hepatitis, end-stage liver disease, lung cancer, and colorectal cancer (12,13). The study also discovered that older individuals with HIV are disproportionately likely to come from potentially underserved communities, including minorities, who make up 49% of older HIV-positive individuals. Additionally, PLWH who are 65 years or older face a higher risk of multiple coexisting medical conditions compared to other beneficiaries of fee-for-service Medicare (14).

As the number of older adults living with HIV in the United States continues to rise, it is crucial to consider the evaluation and management of age-related comorbidities in their clinical treatment. Incorporating elements of palliative care into their overall disease management strategy can significantly improve their quality of life. Acknowledging the complex interplay between aging, long-term management of HIV, and the related psychosocial issues is the initial step towards providing effective palliative care.

Screening for palliative care needs of people aging with HIV

The specialist level palliative care consultation services may not be available at all outpatient settings. Therefore, it is important to incorporate palliative care into practice of geriatricians, primary care providers, and infectious diseases specialists who provide medical care for people aging with HIV. Triggers for a specialist level palliative care consultation for patients with HIV and co-morbid conditions are similar to general criteria for a palliative care consult (see Table 1).

Given the potential stigma and discrimination in older adults with HIV (15), healthcare professionals can try to create a supportive and inclusive environment for terminally ill older patients by addressing the physical, emotional, and social impact while trying to achieve the best possible quality of life (QoL). Mitigating deeply ingrained psychosocial conditions is complex but also necessary to optimize QoL of patients with HIV and advanced illness. Screening for palliative care needs includes identifying individuals who may benefit from palliative care services for symptom management, alleviate high physical burden, provide psychological support, and improve quality of life (16). It is important to note that screening for palliative care does not mean giving up on curative treatments. Palliative care can be provided alongside curative treatments to improve quality of life and provide holistic care. Palliative care specialist teams can help navigate through unique challenges and needs of terminally ill older adults living with HIV. This may include providing support for advance care planning, role of life sustaining treatments in patients with terminal prognosis (17).

Traditional geriatric assessment tools like the Geriatric Depression Scale (GDS) and the Mini-Mental State Examination (MMSE) can help identify psychological and cognitive symptoms that may require attention. The geriatric care model emphasizes a focus on the “5Ms”: mind, mobility, multimorbidity, medications, and matters most, serves as an effective tool for both communication and selecting specific areas for screening and assessment (18). The 5Ms are a useful way to communicate and choose an area for screening (Table 2).

We advise employing the Edmonton Symptom Assessment Scale (ESAS) as a go-to instrument for gauging and continually re-examining symptoms. It is a frequently used tool by palliative care providers. This straightforward numerical scale evaluates nine prevalent symptoms, including pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, overall well-being, and breathlessness. Initially created in 1991, the ESAS has undergone psychometric validation and has been translated into more than 20 languages, with a subsequent revised version (ESAS-r) (19). ESAS-r tool can also be customized for evaluating the symptom burden in HIV patients, assisting in effective symptom management (Figure 1). A thorough pain evaluation can assist in determining the type and severity of the pain, thereby facilitating individualized pain management approaches. Routine assessments of symptoms and functional status can help in the early identification of emerging problems, enabling prompt intervention, and minimizing the worsening of symptoms.

Figure 1 Edmonton Symptom Assessment Scale-Revised. Available at https://www.albertahealthservices.ca/frm-07903.pdf.

The Karnofsky Performance Status (KPS) scale (20) which can aid to assess a patient’s functional status across clinical care settings, can be helpful in determining a patient’s level of independence and functional ability. The KPS functional assessment tool was developed in 1948, enabling physicians to evaluate a patient’s ability to survive cancer chemotherapy. It is widely utilized by Palliative Care Specialists and applied to a wide spectrum of patients with advanced illnesses (Table 3). This instrument can be adapted to account for the unique difficulties and functional constraints experienced by older PLWH and additional chronic conditions.

The Veterans Aging Cohort Study (VACS) 2.0 Index has been utilized to estimate morbidity and mortality risk. Multiple observational studies suggest that this index offers better predictive accuracy compared to both individual and combined indices currently being employed (Table 4). The (VACS) 2.0 Index incorporates factors such as age, standard lab tests including CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate aminotransferase (AST) and alanine transaminase (ALT), estimated glomerular filtration rate (eGFR), albumin and hepatitis C status (Table 4) (21,22). It is recommended for estimating short- and long-term risk of morbidity and mortality, estimating life expectancy, quantifying response to interventions, and detecting HIV and non-HIV treatment toxicity.

Normal aging comes with a gradual reduction in physiological capabilities. The presence of frailty syndrome exacerbates this decline in older individuals (23). Multiple factors make adults with HIV more susceptible to frailty, such as extended duration since HIV diagnosis, low CD4 cell counts, detectable levels of plasma HIV RNA, body mass indices that are either too low or too high, untreated Hepatitis C infections, diabetes, kidney issues, and prolonged use of ART (24,25). Symptoms of frailty can include severe fatigue, frequent falls, and inconsistent mental and physical functioning (26). Frailty is characterized by the existence of three or more of the following five criteria:

• Involuntary weight loss,
• Self-described fatigue,
• Reduced energy output,
• Slowed walking pace, and
• Poor grip strength.

Screening for frailty could provide another useful tool to measure and guide the delivery of palliative care.

Utilizing patient-reported outcome measures (PROMs) serves to evaluate a patient’s health condition at a specific moment, while also encouraging patients to openly share their experiences. This strengthens the patient-healthcare provider bond and fosters individualized care. In the context of PLWH, PROMs have demonstrated their ability to reliably forecast key health outcomes like morbidity, mortality, and healthcare costs. Although there are limited PROMs designed for PLWH, none have been specifically created for aging individuals with HIV (27). Patient-Reported Outcomes Quality of Life-HIV (PROQOL-HIV) has been specifically tailored for HIV patients. It includes domains such as symptoms, treatment impact, and social relationships (28). These tools can serve as starting point for assessing palliative care needs in older patients with HIV.

Common co-morbid conditions increasing morbidity and mortality risk in patients aging with HIV

In the modern ART era, prognostication is complicated by numerous factors. For example, PLWH who are diagnosed and treated early with ART have significantly improved life expectancy compared to those who are diagnosed and treated later (29). Resistance to ART leading to treatment failure is uncommon. Several other factors have been found to correlate with a worse prognosis for individuals living with HIV (21,22). Delayed diagnosis and initiation of treatment can lead to a more advanced stage of HIV infection, resulting in a compromised immune system and higher risk of complications including OIs. Co-infections such as viral hepatitis can accelerate and lead to hepatic complications if not treated. Socioeconomic factors, access to healthcare and inadequate support systems can impact patient’s adherence to treatment and prognosis. One of the most used prognostic tools in patients living with HIV is the VACS Index which combines seven variables to predict mortality in PLWH (Table 4). Most common co-morbid conditions may contribute to increased mortality risk are summarized below.

Cardiovascular disease (CVD)

CVD, such as heart attacks and strokes, rank among the top causes of death for older PLWH, a trend that mirrors the general population. However, it is important to note that PLWH face a higher relative risk for various forms of CVD, typically ranging from 1.5 to 2 times greater, compared to those who are not infected with HIV (30). The underlying causes for this increased risk of cardiovascular diseases in PLWH are complex and likely involve a combination of factors. These include traditional risk elements like high blood pressure and cholesterol, along with HIV-specific contributors such as chronic immune activation and inflammation (31). ART can also introduce its own set of risks, including dyslipidemia and other metabolic complications. Lifestyle choices, like substance use or a lack of physical activity, further compound these risks (32). Additionally, disparities in healthcare access and utilization also play a role in this elevated risk (33).

Cancer

Cancer is the second leading cause of mortality in PLWH. The incidence of AIDS defining malignancies such as Kaposi sarcoma (KS) and non-Hodgkin lymphoma has decreased since the introduction of ART as CD4 counts are improving (34). The risk of KS increases with lower CD4-T cell count. Five-year survival for non-visceral KS is 92% and while that of visceral KS is 82.6% (35).

According to the National Cancer Database (NCDB), over 52,000 PLWH were diagnosed with cancer between the years 2004 and 2018 (36). Compared to their HIV-negative counterparts, these individuals were generally younger, predominantly male, more often insured by Medicaid, lived in lower-income areas, and were less likely to be white. Lung cancer was the most commonly diagnosed cancer among both PLWH and HIV-negative adults. Other cancers that were frequently diagnosed in PLWH included diffuse large B-cell lymphoma (DLBCL) at 16%, KS at 11%, and colorectal, anal, and prostate cancers at 11% and 8%, respectively (37).

In terms of cancer staging, PLWH were more likely to receive a stage IV diagnosis compared to HIV-negative adults (32% vs. 19%, P<0.001). Interestingly, only 5% of PLWH diagnosed with cancer received palliative care, although they were 25% more likely to receive such care compared to HIV-negative individuals. Despite advances in ART that have reduced the overall risk of many HIV-associated cancers, older PLWH still face a higher likelihood of not only developing these cancers but also succumbing to them (37,38).

Neurocognitive disorders

Neurological issues linked to HIV, including HIV-associated neurocognitive disorders (HAND) and central nervous system (CNS) OIs, are significant factors that can exacerbate morbidity and mortality among older adults living with HIV (39). Multiple research efforts centered on people with HIV have identified an array of contributing elements that lead to cognitive deterioration. These factors encompass frailty, a low baseline CD4 cell count, the presence of HIV RNA in blood plasma, previous injuries to the CNS, and assorted coexisting conditions such as viral hepatitis, psychiatric illness, and substance abuse disorders (40-42).

Kidney disease

Chronic kidney disease poses a significant risk for older PLWH, particularly those who have experienced antiretroviral drug toxicity or have other medical conditions that impair kidney function. Besides older age, which is a key predictor of chronic kidney disease in adults with HIV, other contributing factors include the use of the drug tenofovir disoproxil fumarate (TDF), being female, having diabetes or hypertension, untreated hepatitis C infection, a history of injecting drugs, prior acute kidney injury, lower CD4 cell counts, and elevated HIV RNA levels (43).

OIs

Older PLWH tend to exhibit a blunted immunological response to ART, leading to a persistent risk of OIs despite viral suppression. Common OIs such as Pneumocystis jirovecii pneumonia, Toxoplasma gondii encephalitis, and Mycobacterium avium complex, once rampant, are now less frequent but still require vigilance. The treatment of OIs in this population necessitates a nuanced approach, balancing the need for efficacy with the potential for drug-drug interactions and the management of co-existing age-related conditions (44,45).

Causes of death in older adults patients with HIV

The causes of death in older patients with HIV in the United States have evolved over time as HIV transitioned to a chronic illness. From 2010 to 2018, there was an overall decrease in death rates by 36.6%. The rates of deaths directly related to HIV dropped by 48.4%, while deaths not related to HIV saw a reduction of 8.6%. When examined by race or ethnicity in the year 2017, the highest rates of HIV-related deaths were observed among individuals of multiple races (7.0 per 100,000), followed by Black/African American individuals (5.6 per 100,000). White and Hispanic/Latino individuals had similar rates at (3.9 per 100,000) (46). It’s important to note that the causes of death can vary based on factors such as individual health status, access to healthcare, treatment adherence, and social determinants of health.

Pain and symptom assessment and management

The patients with HIV often experience a diverse range of symptoms that result from a combination of the virus itself, its treatments, and the normal aging process is potentially accelerated in PLWH. Common symptoms include physical discomfort such as pain, fatigue, gastrointestinal disturbances, and neurological complications (47). Additionally, psychosocial symptoms including depression, anxiety, cognitive impairments, and social isolation can significantly impact the overall well-being of this population.

Pain is one of the most reported symptoms and under treated due to fear of addiction from patient and providers, medication side effects. PLWH are more likely to have chronic pain, receive opioid analgesic treatment, receive higher doses of opioids, and have co-morbid conditions such as substance use disorders and mental illness compared with the general population (48,49). The most common pain syndromes in older patients with HIV includes polyneuropathy, antiretroviral toxic neuropathy (ATN). The clinical features of these neuropathies are often dominated by painful dysesthesia, allodynia, and hyperalgesia (Table 5). The onset is often gradual, beginning with bilateral lower extremity involvement and progressing in a length-dependent fashion. Management of chronic pain in PLWH can be complex and recommended practice for treatment of chronic pain in PLWH is similar to noninfected patients (50,51). The limited data on chronic opioid treatment in PLWH is conflicting regarding its effect on adherence with ART. Buprenorphine recommended in high-risk patients which may help to improve pain and increase compliance with disease modifying treatments (52). In Table 6, the current Centers for Disease Control (CDC) guidelines for prescribing opioids for chronic pain in the United States are summarized (52,53) and applicable to older PLWH and chronic pain. PLWH with greater depressive symptoms experience more pain than those with fewer depressive symptom (54). Older PLWH presenting with chronic pain and depression will benefit from multidisciplinary approach including behavioral health and patients with complex pain syndromes should be consulted with palliative care, and pain medicine specialists.

Fatigue is another prevalent symptom among patients and significantly affects both their quality of life and emotional well-being (55). Fatigue has been linked to anemia, malnutrition secondary to malabsorption or decrease nutritional intake or wasting due to diarrhea, HIV-associated dementia, HIV myopathy, and pain and sleep disturbances in pre-ART era (56). In the ART era, PLWH are a population may be affected by fatigue due to risk factors associated with HIV-infection, co-morbidities, treatment, and psychosocial disease burden. Treatment of fatigue should be focused on the underlying cause. Clinical and pharmacological options include supplements to address hormone imbalances and anemia and to improve nutritional deficiencies that cause fatigue.

Comprehensive symptom assessments serve as a guide for optimizing pain and symptom management and enhancing the patient’s quality of life. This might include medication adjustments, opioid risk assessment, pain management strategies, psychotherapy, and resource utilization.

Challenges in advance care planning

In the initial stages of the HIV epidemic, before the advent of effective ART, end-of-life care and early-stage advanced care planning were standard components of clinical management for PLWH; however, as PLWH are now living longer and healthier lives, the focus on advanced care planning has diminished and is frequently neglected in regular HIV primary care (57). We advise healthcare providers who are treating older PLWH with advanced medical conditions to engage in conversations about end-of-life choices. These conversations may help patients to appoint a durable power of attorney for healthcare matters and to fill out state-specific advance healthcare directives, such as Physicians (Medical) Orders for Life Sustaining Treatment (POLST/MOLST) forms, to clearly outline their end-of-life care preferences. Challenges may arise concerning the disclosure of the patient’s HIV status to their adult children, which can complicate both caregiving and advanced care planning. When considering the option to withhold treatments, it is crucial to approach the matter delicately, ensuring that the patient’s autonomy and personal wishes are honored.

One of the most difficult decisions that will need to be made by physicians, patients, and family members is when is the time to stop ART at the end of life. There are no established guidelines for discontinuing ART when a patient is nearing the end of their life. On the other hand, continuing ART in patients with life limiting illness is an important aspect of comprehensive end of life care. Unfortunately, despite its well-established benefits, the number of PLWH in nursing homes receiving ART is less than optimal. In one study, only 36% of nursing home patients received any ART regimen during an average of about 1 year of observation (58). The exclusion of ART did not significantly vary based on whether a resident was at the end of life. While the primary goal of ART is to suppress viral replication and preserve immune function, it can continue to provide substantial benefits at the end of life including improved quality of life, prolonging survival, and the mitigation of HIV-related complications. For example, by reducing the risk of OIs, ART can, in turn, alleviate symptoms and enhance a patient’s overall well-being at the end of life. Moreover, by preserving immune function, it reduces the likelihood of additional infections, minimizing the burden on patients already facing significant health challenges. ART also helps to destigmatize HIV, as it underscores the commitment to treating every patient with dignity and respect, regardless of their prognosis. It also serves as a reminder to both patients and healthcare providers that even in the face of a terminal illness, an emphasis should be placed on patient comfort. Although concerns surrounding potential side effects and complexities of ART were common in the past, most PLWH, including those at the end of life, can be maintained on a straightforward, well-tolerated regimen.

Hospice care

Hospice care is centered around end-of-life stages, typically for patients with a prognosis of six months or less to live. The hospice team offers comprehensive support to help patients transition through the dying process, while also guiding their families during these challenging times. Trained hospice professionals in grief counseling provide bereavement services to the families, extending up to 13 months following the patient’s death. Inequalities in accessing hospice care are a significant concern. Historically, hospice populations have predominantly consisted of white, middle-class, cancer patients. Several barriers impede equitable access: prognostic uncertainty, institutional cultures, specific needs of diverse groups, and limited public awareness of Medicare Hospice benefit (59). These challenges continue to confront the hospice movement in its efforts to ensure equal access for everyone.

In the modern landscape of ART, often comorbid conditions, not HIV, which serve as the main catalyst for hospice referrals. Medicare criteria for hospice eligibility (general and disease specific criteria) summarized in Table 7 (60).

Conclusions

The population aging with HIV has been increasing due to transformation of HIV/AIDS from a terminal disease to a chronic illness in the United States. Cardiovascular disease and cancer are leading causes of death in older PLWH. People aging with HIV experience a unique intersection of age-related challenges, comorbid conditions, and the complexities of a historically stigmatized illness. Primary care providers and geriatric specialists can assist by addressing patient’s most important concerns as a starting point for advanced care planning. Every office visit presents a chance to reassess care objectives and delve into emotional stressors, financial hurdles, and formulate approaches to help patients surmount these obstacles. Through effective symptom control and streamlined care coordination, health care professionals can significantly improve the quality of life for people aging with HIV who are also dealing with terminal conditions. Although palliative and hospice care are proven to enhance patients’ quality of life, their use remains limited. This underutilization is partially due to various factors, such as a lack of awareness and misconceptions among patients and caregivers about these services. Utilizing resources such as the Medicare Hospice benefit when appropriate can be a valuable addition to their overall care strategy. Continued research is crucial for fine-tuning assessment, developing validated, user-friendly screening instruments, and establishing guidelines for palliative care that are specifically designed for the expanding demographic of older PLWH with multiple coexisting conditions. Well conducted studies are needed to study populations aging with HIV with non-malignant diseases and mixed diagnoses, symptom burden, achieving patient preferred place of care, patient satisfaction with care, caregiver outcomes (satisfaction with care, burden, depression, anxiety, grief, quality of life) by comparing standard care with palliative care integrated geriatric care models (61).

Acknowledgments

We extend our heartfelt gratitude to Anjali Sharma, MD, MS, Professor of Medicine at the Albert Einstein College of Medicine, Bronx, NY encompassing the Divisions of General Internal Medicine and Infectious Diseases. Her invaluable guidance and insightful critiques have been instrumental in shaping this manuscript.

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by Guest Editors (Pragnesh Patel, Susan Nathan and Lara Skarf) for the series “Outpatient Palliative Care in Geriatric Clinics” published in Annals of Palliative Medicine. The article has undergone external peer review.

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-23-550/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-23-550/coif). The series “Outpatient Palliative Care in Geriatric Clinics” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Xia Q, Maduro GA, Li W, et al. Life Expectancy Among People With HIV in New York City, 2009-2018. J Acquir Immune Defic Syndr 2022;91:434-8. [Crossref] [PubMed]
2. Centers for Disease Control and Prevention. Diagnoses of HIV infection in the United States and Dependent Areas, 2021. HIV Surveillance Report, 2021; vol. 34. Available online: https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-34/index.html
3. Vance DE, Cody SL. Predictions of geriatric HIV in 2030. Lancet Infect Dis 2015;15:753-4. [Crossref] [PubMed]
4. Longenecker CT, Sullivan C, Baker JV. Immune activation and cardiovascular disease in chronic HIV infection. Curr Opin HIV AIDS 2016;11:216-25. [Crossref] [PubMed]
5. Tricco AC, Lillie E, Zarin W, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med 2018;169:467-73. [Crossref] [PubMed]
6. Croxford S, Kitching A, Desai S, et al. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort. Lancet Public Health 2017;2:e35-46. [Crossref] [PubMed]
7. Farahani M, Mulinder H, Farahani A, et al. Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis. Int J STD AIDS 2017;28:636-50. [Crossref] [PubMed]
8. Reddy KP, Parker RA, Losina E, et al. Impact of Cigarette Smoking and Smoking Cessation on Life Expectancy Among People With HIV: A US-Based Modeling Study. J Infect Dis 2016;214:1672-81. [Crossref] [PubMed]
9. Chen C, Cao X, Xu J, et al. Comparison of healthspan-related indicators between adults with and without HIV infection aged 18-59 in the United States: a secondary analysis of NAHNES 1999-March 2020. BMC Public Health 2023;23:814. [Crossref] [PubMed]
10. Althoff KN, Justice AC, Gange SJ, et al. Virologic and immunologic response to HAART, by age and regimen class. AIDS 2010;24:2469-79. [Crossref] [PubMed]
11. Zhang Q, Yu X, Wu T, et al. Immunological and Virological Responses in Older HIV-Infected Adults Receiving Antiretroviral Therapy: An Evidence-Based Meta-Analysis. J Acquir Immune Defic Syndr 2020;83:323-33. [Crossref] [PubMed]
12. Turrini G, Chan SS, Klein PW, et al. Assessing the health status and mortality of older people over 65 with HIV. PLoS One 2020;15:e0241833. [Crossref] [PubMed]
13. Althoff KN, McGinnis KA, Wyatt CM, et al. Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis 2015;60:627-38. [Crossref] [PubMed]
14. Friedman EE, Duffus WA. Chronic health conditions in Medicare beneficiaries 65 years old, and older with HIV infection. AIDS 2016;30:2529-36. [Crossref] [PubMed]
15. Brown MJ, Adeagbo O. HIV and Aging: Double Stigma. Curr Epidemiol Rep 2021;8:72-8. [Crossref] [PubMed]
16. Simms V, Higginson IJ, Harding R. Integration of palliative care throughout HIV disease. Lancet Infect Dis 2012;12:571-5. [Crossref] [PubMed]
17. Fausto JA Jr, Selwyn PA. Palliative care in the management of advanced HIV/AIDS. Prim Care 2011;38:311-26. ix. [Crossref] [PubMed]
18. Tinetti M, Huang A, Molnar F. The Geriatrics 5M's: A New Way of Communicating What We Do. J Am Geriatr Soc 2017;65:2115. [Crossref] [PubMed]
19. Hui D, Bruera E. The Edmonton Symptom Assessment System 25 Years Later: Past, Present, and Future Developments. J Pain Symptom Manage 2017;53:630-43. [Crossref] [PubMed]
20. Crooks V, Waller S, Smith T, et al. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J Gerontol 1991;46:M139-44. [Crossref] [PubMed]
21. Tate JP, Sterne JAC, Justice AC, et al. Albumin, white blood cell count, and body mass index improve discrimination of mortality in HIV-positive individuals. AIDS 2019;33:903-12. [Crossref] [PubMed]
22. VACS Index Information and VACS Calculator. Available online: https://www.mdcalc.com/calc/10402/veterans-aging-cohort-study-vacs-2.0-index
23. Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet 2013;381:752-62. [Crossref] [PubMed]
24. Brothers TD, Kirkland S, Guaraldi G, et al. Frailty in people aging with human immunodeficiency virus (HIV) infection. J Infect Dis 2014;210:1170-9. [Crossref] [PubMed]
25. Brañas F, Torralba M, Antela A, et al. Effects of frailty, geriatric syndromes, and comorbidity on mortality and quality of life in older adults with HIV. BMC Geriatr 2023;23:4. [Crossref] [PubMed]
26. Lellouche L, Gutierrez LA, Leclercq P, et al. Brief Report: Frailty in Aging People Living With HIV: A Matched Controlled Study. J Acquir Immune Defic Syndr 2021;88:305-9. [Crossref] [PubMed]
27. Kall M, Marcellin F, Harding R, et al. Patient-reported outcomes to enhance person-centred HIV care. Lancet HIV 2020;7:e59-68. [Crossref] [PubMed]
28. Duracinsky M, Lalanne C, Le Coeur S, et al. Psychometric validation of the PROQOL-HIV questionnaire, a new health-related quality of life instrument-specific to HIV disease. J Acquir Immune Defic Syndr 2012;59:506-15. [Crossref] [PubMed]
29. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV 2017;4:e349-56. [Crossref] [PubMed]
30. Shah ASV, Stelzle D, Lee KK, et al. Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis. Circulation 2018;138:1100-12. [Crossref] [PubMed]
31. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 2011;62:141-55. [Crossref] [PubMed]
32. Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med 2013;173:614-22. [Crossref] [PubMed]
33. Menza TW, Hixson LK, Lipira L, et al. Social Determinants of Health and Care Outcomes Among People With HIV in the United States. Open Forum Infect Dis 2021;8:ofab330. [Crossref] [PubMed]
34. Biggar RJ, Chaturvedi AK, Goedert JJ, et al. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst 2007;99:962-72. [Crossref] [PubMed]
35. Hleyhel M, Belot A, Bouvier AM, et al. Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort. Int J Cancer 2015;137:2443-53. [Crossref] [PubMed]
36. Islam JY, Nogueira L, Suneja G, et al. Palliative Care Use Among People Living With HIV and Cancer: An Analysis of the National Cancer Database (2004-2018). JCO Oncol Pract 2022;18:e1683-93. [Crossref] [PubMed]
37. Silverberg MJ, Lau B, Achenbach CJ, et al. Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study. Ann Intern Med 2015;163:507-18. [Crossref] [PubMed]
38. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS 2009;23:2337-45. [Crossref] [PubMed]
39. Rodriguez-Penney AT, Iudicello JE, Riggs PK, et al. Co-morbidities in persons infected with HIV: increased burden with older age and negative effects on health-related quality of life. AIDS Patient Care STDS 2013;27:5-16. [Crossref] [PubMed]
40. Sun-Suslow N, Paolillo EW, Morgan EE, et al. Brief Report: Frailty and HIV Disease Severity Synergistically Increase Risk of HIV-Associated Neurocognitive Disorders. J Acquir Immune Defic Syndr 2020;84:522-6. [Crossref] [PubMed]
41. Aung HL, Aghvinian M, Gouse H, et al. Is There Any Evidence of Premature, Accentuated and Accelerated Aging Effects on Neurocognition in People Living with HIV? A Systematic Review. AIDS Behav 2021;25:917-60. [Crossref] [PubMed]
42. Gonzalez JS, Batchelder AW, Psaros C, et al. Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr 2011;58:181-7. [Crossref] [PubMed]
43. Razzak Chaudhary S, Workeneh BT, Montez-Rath ME, et al. Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy. Nephrol Dial Transplant 2015;30:1734-40. [Crossref] [PubMed]
44. Masur H, Read SW. Opportunistic Infections and Mortality: Still Room for Improvement. J Infect Dis 2015;212:1348-50. [Crossref] [PubMed]
45. Marcus JL, Leyden W, Anderson AN, et al. Increased overall life expectancy but not comorbidity-free years for people with HIV [abstract 151]. Presented at the 2020 Conference on Retroviruses and Opportunistic Infections; March 8–11, 2020; Boston, Massachusetts. Available online: https://www.croiconference.org/abstract/increased-overall-life-expectancy-but-not-comorbidity-free-years-for-people-with-hiv/
46. Bosh KA, Johnson AS, Hernandez AL, et al. Vital Signs: Deaths Among Persons with Diagnosed HIV Infection, United States, 2010-2018. MMWR Morb Mortal Wkly Rep 2020;69:1717-24. [Crossref] [PubMed]
47. Wilson NL, Hoffman TJ, Heath SL, et al. HIV Symptom Clusters are Similar Using the Dimensions of Symptom Occurrence and Distress. J Pain Symptom Manage 2022;63:943-52. [Crossref] [PubMed]
48. Merlin JS, Cen L, Praestgaard A, et al. Pain and physical and psychological symptoms in ambulatory HIV patients in the current treatment era. J Pain Symptom Manage 2012;43:638-45. [Crossref] [PubMed]
49. Tsao JC, Plankey MW, Young MA. Pain, psychological symptoms and prescription drug misuse in HIV: A literature review. J Pain Manag 2012;5:111-8. [PubMed]
50. Bruce RD, Merlin J, Lum PJ, et al. 2017 HIV Medicine Association of Infectious Diseases Society of America Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With Human Immunodeficiency Virus. Clin Infect Dis 2017;65:1601-6. [Crossref] [PubMed]
51. Lewis Ramos V, Eti S. Assessment and Management of Chronic Pain in the Seriously Ill. Prim Care 2019;46:319-33. [Crossref] [PubMed]
52. Cunningham CO. Opioids and HIV Infection: From Pain Management to Addiction Treatment. Top Antivir Med 2018;25:143-6. [PubMed]
53. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA 2016;315:1624-45. [Crossref] [PubMed]
54. Derry-Vick HM, Johnston CD, Brennan-Ing M, et al. Pain Is Associated With Depressive Symptoms, Inflammation, and Poorer Physical Function in Older Adults With HIV. Psychosom Med 2022;84:957-65. [Crossref] [PubMed]
55. Barroso J, Leserman J, Harmon JL, et al. Fatigue in HIV-Infected People: A Three-Year Observational Study. J Pain Symptom Manage 2015;50:69-79. [Crossref] [PubMed]
56. Breitbart W, McDonald MV, Rosenfeld B, et al. Fatigue in ambulatory AIDS patients. J Pain Symptom Manage 1998;15:159-67. [Crossref] [PubMed]
57. Barocas JA, Erlandson KM, Belzer BK, et al. Advance directives among people living with HIV: room for improvement. AIDS Care 2015;27:370-7. [Crossref] [PubMed]
58. Zhang T, Shireman TI, Meyers DJ, et al. Use of antiretroviral therapy in nursing home residents with HIV. J Am Geriatr Soc 2022;70:1800-6. [Crossref] [PubMed]
59. Tobin J, Rogers A, Winterburn I, et al. Hospice care access inequalities: a systematic review and narrative synthesis. BMJ Support Palliat Care 2022;12:142-51. [Crossref] [PubMed]
60. Centers for Medicare & Medicaid Services. Local Coverage Determination (LCD) for Hospice Determining Terminal Status (L33393, L34538). (Accessed on January 26, 2023).
61. Kokorelias KM, Grosse A, Zhabokritsky A, et al. Understanding geriatric models of care for older adults living with HIV: a scoping review and qualitative analysis. BMC Geriatr 2023;23:417. [Crossref] [PubMed]