Care of the Aging Patient: From Evidence to Action; Mgt of HIV+ in Advanced Age
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April 3, 2013
Management of Human Immunodeficiency Virus Infection in Advanced Age
Meredith Greene, MD; Amy C. Justice, MD, PhD; Harry W. Lampiris, MD; Victor Valcour, MD
"management of aging HIV-positive patients is a relatively recent clinical problem clinicians worldwide must address.....older HIV-positive adults commonly live alone and may score higher on social isolation scales
"Once patients have achieved viral suppression and are tolerating therapy, treatment priorities transition to managing comorbid non-HIV medical conditions, risk reduction, and preventive care"
"for older HIV-positive patients, there are new challenges with polypharmacy and comorbidity. We conceptualize the care of older HIV-positive patients into 3 stages: early care, which focuses on HIV screening, diagnosis, and initiation of treatment; chronic care, which emphasizes maintenance of HIV treatment and management of non-HIV comorbidities; and advanced care, which considers goals of care and end-of-life planning."
"Mr H is a 74-year-old man.....He has hypertension, hyperlipidemia, osteoporosis, depression, atherosclerotic subclavian steal syndrome with stent placement, chronic kidney insufficiency, adenomatous colon polyps, and past anal squamous cell carcinoma......Mr H was a computer systems analyst until his late 40s when he was diagnosed with HIV.....As evidenced by his age, increasing fatigue, and weight loss, Mr H may be reaching a crossroad. A single insult such as a fall, an episode of pneumonia, or an adverse drug event might shatter this patient's independence. Compared with when he was diagnosed with HIV, achieving excellent antiretroviral medication adherence and overcoming toxicities are no longer the major priorities for his care. For an HIV-uninfected individual similar to Mr H but without weight loss, life expectancy approximates 10 years."
The transition of HIV infection from a terminal illness to a chronic manageable disease demonstrates the considerable gains in HIV treatment. Given these successes, management of aging HIV-positive patients is a relatively recent clinical problem clinicians worldwide must address. While HIV-positive patients have much in common with HIV-negative patients who are aging with attendant chronic diseases, issues of polypharmacy, care integration, social isolation, and end-of-life planning are complicated by HIV. A comprehensive care approach integrating principles from geriatric medicine is needed to manage the care of patients coping with multiple comorbid medical diseases. Optimal models of care must be identified—with HIV specialists, primary care clinicians, and geriatricians working together to make successful aging for this population achievable.
"Maximizing everyday function is a major objective when treating aging HIV-positive patients. Chronic health conditions in HIV are associated with lower self-reported physical, social, and mental health functioning as assessed by SF-36 testing.44 The combination of HIV and age may adversely affect performance of instrumental activities of daily living."
THE PATIENT'S STORY
Mr H is a 74-year-old man who was diagnosed with human immunodeficiency virus (HIV) in 1984. He has chronic fatigue and has experienced a 10-lb weight loss over the past 2 years. His current CD4+ T-lymphocyte count is 440 cells/μL, with a nadir of 140 cells/μL occurring in 1991. He has never had opportunistic infections. His plasma HIV RNA level (viral load) has been undetectable since 1996. Mr H participated in the original zidovudine (AZT) monotherapy clinical trial in 1988 and subsequently received a total of 7 nucleoside reverse transcriptase inhibitors (NRTIs) and 6 protease inhibitors before starting his current regimen of emtricitabine/tenofovir and ritonavir-boosted fosamprenavir. He receives treatment at an infectious disease clinic in an urban, tertiary care Veterans Affairs hospital, where his follow-up is led by Dr L and a team that includes an infectious diseases pharmacist, a nutritionist, and a social worker.
Mr H vigilantly adheres to his antiretroviral regimen. Even when offered new antiretroviral medications, he prefers to stay with his current regimen. He has hypertension, hyperlipidemia, osteoporosis, depression, atherosclerotic subclavian steal syndrome with stent placement, chronic kidney insufficiency, adenomatous colon polyps, and past anal squamous cell carcinoma. His other medications are rosuvastatin (hyperlipidemia), testosterone (low testosterone level), bupropion (depression), fenofibrate (hypertriglyceridemia), and lorazepam (anxiety; taken as needed). Due to episodic dizziness and fluctuating blood pressure, hydrochlorothiazide and metoprolol were recently discontinued.
Mr H was a computer systems analyst until his late 40s when he was diagnosed with HIV. He lives with a partner, but voices concerns for social isolation from the deaths of many HIV-positive acquaintances. He participates in a support group of older adults with HIV run by a psychologist. Mr H is a former smoker and drinks a glass of wine with dinner. He never drank alcohol heavily and never used recreational drugs. He is currently not sexually active.
Initial evaluation of his fatigue and weight loss revealed no anemia and his pharmacist found no medication-based association with his symptoms. Dr L discussed testing for malignancy or other disorders causing weight loss, but Mr H initially declined. Mr H retains medical decision-making capacity and has specified that he not receive resuscitation or intubation should he experience a cardiopulmonary arrest.
Mr H and Dr L were interviewed by a Care of the Aging Patient editor in 2012.
Mr H:When you got HIV in those days it was a death sentence. That was what was expected—you would die. To live even 5 years was a surprise to me.
Dr L: (I met Mr H) about 7 years ago . . . His HIV needs were fairly well controlled. But he was already middle aged and experiencing middle-aged types of medical issues. HIV is still something we address at each of our appointments but it really has retreated into the background.
PUTTING MR H'S CARE INTO CONTEXT
Aging of the HIV-positive population is an unexpected development in the history of the HIV/AIDS epidemic. The first US case of HIV-1 was reported more than 3 decades ago. Progressive immunodeficiency with opportunistic infections, AIDS-related malignancies, and death were hallmark features until the mid-1990s when combination antiretroviral therapy (ART) produced durable reductions in mortality. Medication improvements resulted in better tolerability and reduced pill burden, which facilitated adherence with sustained immunologic and virologic responses. By 2005, a 20-year-old HIV-positive noninjection drug user from a high-income country could expect to live to age 65 years.1 Longer life expectancy is seen in all settings where there is access to combination ART; it is estimated that one-half of HIV-positive individuals in the United States will be older than age 50 by 2015. Eleven percent of incident infections in the United States between 2006 and 2009 occurred among individuals older than age 50.2 In the United States, HIV rates for older African Americans are 12 times higher than that of older white individuals and 70% of older HIV-positive women are African American or Hispanic/Latina.3,4
In the modern era (since combination ART), AIDS has evolved into a chronic disease, and for older HIV-positive patients, there are new challenges with polypharmacy and comorbidity. We conceptualize the care of older HIV-positive patients into 3 stages: early care, which focuses on HIV screening, diagnosis, and initiation of treatment; chronic care, which emphasizes maintenance of HIV treatment and management of non-HIV comorbidities; and advanced care, which considers goals of care and end-of-life planning.
Treatment should consider that HIV-associated non-AIDS conditions are more likely to impact mortality than HIV
Management of comorbidities should be prioritized (especially cardiovascular, hepatic, renal, bone, central nervous system)
Modifiable lifestyle risk factors, focusing on health maintenance and prevention, should be addressed
Risk for polypharmacy and drug-drug interactions in older HIV-positive adults should be considered
Risk for social isolation in older HIV-positive adults should be considered because social support can impact health outcomes
Palliative care is reemerging as an important component in older HIV-positive patients
Best models of care are not well defined but will require integration of HIV, primary care, and geriatric expertise
Chronic- and Advanced-Stage Care
Prognosis becomes an increasingly important component of decision making related to screening, adding medications, and considering invasive treatments
Ongoing discussions and documentation of end-of-life preferences, choice of living environment, and safety should be completed
Maintenance (Chronic-Care) Stage
Mr H:[HIV has] completely evolved into a manageable disease and I don't dwell on it; I live life like I don't have HIV.
Dr L:Clinicians increasingly [realize that having] HIV, even when it's well controlled, can impact other conditions including cardiovascular disease. The challenges of managing [treatment in] HIV patients are probably not so different than the management of [treatment in] other aging patients with multiple medical problems.
Once patients have achieved viral suppression and are tolerating therapy, treatment priorities transition to managing comorbid non-HIV medical conditions, risk reduction, and preventive care (Box). These priorities include appropriately indicated screening examinations that are recommended for patients of a particular age. Disease screening itself can confer risk and may uncover conditions that require treatments associated with risks. Identification of new diseases may result in the addition of more medications, worsening polypharmacy in an already complex patient. Before embarking on screening, the consequences of treating newly diagnosed disease entities must be carefully considered.
Comorbid medical conditions:. In the combination ART era, the proportion of AIDS-related deaths declined, while non-AIDS associated mortality increased. Large cohort studies have shown an association between the risk of non-AIDS conditions and CD4+ T-lymphocyte count.30,31 A randomized trial of combination ART treatment interruption was terminated early because treatment interruption not only increased the risk of AIDS-related events, but also cardiovascular, renal, and hepatic events.32 HIV appears to increase the risk of many non-HIV conditions resulting in the use of a new term, HIV-associated non-AIDS (HANA) conditions. HANA conditions are illnesses, such as cardiovascular disease, associated with or exacerbated by HIV infection but are not AIDS-defining conditions (eg, opportunistic infections and AIDS malignancies).17,33 HANA conditions occur more frequently or are more severe with lower CD4+ T-lymphocyte counts or detectable viral loads, but can persist or develop among individuals with suppressed viral loads and high CD4+ T-lymphocyte counts. Although associated with HIV infection, HANA conditions have a multifactorial etiology including the long-term effects of HIV and preexisting coinfections, health behaviors (eg, substance use), and HIV treatments (Table 3).
Common preexisting coinfections contributing to HANA conditions include hepatitis B and hepatitis C viruses (liver cirrhosis and hepatoma) and human papilloma virus (cervical and anal cancer).34,35 Hepatitis C is responsible for more than 90% of liver-related deaths in HIV-positive patients.36 The prevalence of human papillomavirus varies by demographic group, but may be greater than 90% in HIV-positive men who have sex with men.37 HANA conditions are responsible for as many as 60% of deaths in developed-world HIV-positive cohorts, particularly from cardiovascular events, non-AIDS malignancies, and end-stage liver and kidney disease.38 Addressing reversible risk factors through smoking cessation and hyperlipidemia treatment is associated with risk reduction for cardiovascular disease, providing management opportunities.39
Assessing the relative contributions of HIV infection, combination ART, and traditional risk factors to the development of HANA conditions is difficult because HIV-positive and HIV-negative populations in research studies frequently have different behavioral risk factors and comorbid disease burden. Cohort studies suggest an increased risk for cardiovascular disease in HIV-positive patients but did not always fully control for traditional risk factors.40 However, a recent study comparing demographically and behaviorally similar HIV-positive and HIV-negative adults showed substantial excess risk for acute myocardial infarction in the HIV-positive group after adjusting for Framingham risk factors, comorbidities, and substance use.41 Meta analyses comparing HIV-positive patients with HIV-negative groups have shown increased risk of other comorbid diseases often associated with aging, including malignancies and osteoporosis.42,43
Functional Status. Maximizing everyday function is a major objective when treating aging HIV-positive patients. Chronic health conditions in HIV are associated with lower self-reported physical, social, and mental health functioning as assessed by SF-36 testing.44 The combination of HIV and age may adversely affect performance of instrumental activities of daily living.45 The Veteran's Aging Cohort Study (VACS) compared function among demographically matched HIV-infected and noninfected veterans, which found that overall function (measured by a 12-question self report) was comparable. A 50-year-old HIV-positive individual and a 51.5-year-old uninfected individual have comparable function, but comorbidity was a stronger predictor of diminished physical function and disability than age, regardless of HIV status.46 In the Multicenter AIDS Cohort Study, a frailty-related phenotype of weight loss, exhaustion, slowness, and low physical activity was more common in enrollees with HIV infection compared with those who did not have HIV infection, and it predicted mortality independently of CD4 T-lymphocyte count and viral load. But only a small number of individuals exhibited this frailty-related phenotype.47,48
Polypharmacy. Having recently discontinued 2 antihypertensive therapies, Mr H now takes 9 medications including 4 antiretrovirals, 2 lipid-lowering agents, testosterone, an antidepressant, and an anxiolytic. In the Swiss Cohort Study, 14% of HIV-positive participants older than age 65 were taking 4 or more non-HIV medications.49 Common classes of drugs include antihypertensive therapies, lipid-lowering agents, antiplatelet medications, antidepressants, anxiolytic/sedatives, non-HIV-related antiinfective medications, and analgesics.50,51 Supplements and herbal medications used by patients worsen this situation. In recent years, single-pill fixed-combination antiretroviral therapy has decreased pill burden for HIV treatment, a benefit offset by increased use of nonantiretroviral medications.52
Polypharmacy, defined as taking 5 or more chronic medications, is associated with adverse drug events, drug interactions, inappropriate medication use, delirium, falls, fractures, and poor medication adherence.53 Criteria for inappropriate medication use in the general population exist; but, applicability among patients with HIV is unknown. Complex cytochrome P450 inhibition and induction effects, especially with protease inhibitors and nonnucleoside reverse transcriptase inhibitors, as well as effects on P-glycoprotein and other drug transporters, increase risk for interactions (Table 4).27 Medication interactions can be quickly assessed using DHHS guidelines, drug interactions databases,54 or drug interaction software.
Psychosocial Issues and Social Isolation. Social support and the psychosocial context of patients' lives are central to both HIV and geriatric care. While older HIV-positive adults commonly live alone and may score higher on social isolation scales, the size of their social networks and the amount of support they receive from family and friends can be similar to that of younger HIV-positive individuals.55 Nondisclosure, fear of HIV-related stigma, and a desire to be self reliant are self-perceived barriers to accessing social support; but these factors vary greatly due to the heterogeneity of older HIV-positive adults by race/ethnicity, sex/gender, length of infection, and route of exposure.55,56 Loss of friends from AIDS further decreases support networks.57
Self-perceived support and loneliness are linked to health outcomes in older adults who are HIV-negative and may become a determinant for HIV-positive individuals as they age. In HIV, social support is linked to mood, well-being, and medication adherence.58,59 Nonpharmacologic support groups, such as those in which Mr H participates, can ameliorate depression.60 Life experiences result in improved coping strategies and resilience compared with younger patients, despite higher rates of comorbidity and psychosocial challenges.61
Health Care Maintenance and Prevention. The Infectious Diseases Society of America's HIV Primary Care Guidelines recommend following age-appropriate primary care screening guidelines as for the general population.29 For an individual of Mr H's age, grade A and B recommendations from the US Preventive Services Task Force support screening for colorectal cancer, hypertension, depression, and hyperlipidemia; aspirin to prevent cardiovascular disease; smoking and alcohol screening and counseling; healthy diet counseling if cardiovascular risk factors are present; obesity screening and counseling; behavioral counseling for sexually transmitted infections; and diabetes screening if systolic blood pressure exceeds 135/80 mm Hg.62
Caution is needed before applying screening and disease-specific practice guidelines for older patients with multiple comorbid diseases and polypharmacy since complications from treating those diseases or adding to the complexity of an older patient's medication requirements may outweigh benefits. Patients' overall goals and life expectancy should also be considered. Validated geriatric risk assessment tools incorporate measures of cognitive and physical functioning, symptoms, clinical diagnoses, and laboratory values to assess mortality risk63; but the accuracy for these assessments in HIV is not known.
The Veterans Aging Cohort Study (VACS) developed an index that has been validated among cohorts from Europe and North America and is more accurate at predicting all-cause mortality (AIDS, non-AIDS, and cardiovascular) than age, CD4 T-lymphocyte count, and viral load alone.64,65Building on typical HIV measures (CD4, viral load), it also includes routinely monitored indicators of organ system function including hemoglobin, platelet count, transaminases, creatinine, and hepatitis C serology. The VACS Index also predicts morbidities such as hospitalization and fragility fractures and is correlated with functional performance.66,67
Dr L:We have little mini goals-of-care discussions at every visit. [For example,] Mr H actually has a lot of insight about what he's gone through and what he's willing to go through. During his last visit, we broached the idea of doing imaging to determine whether there could be a malignancy or something that would be responsible for his weight loss. He really felt that he didn't want to pursue that at this time.
As evidenced by his age, increasing fatigue, and weight loss, Mr H may be reaching a crossroad. A single insult such as a fall, an episode of pneumonia, or an adverse drug event might shatter this patient's independence. Compared with when he was diagnosed with HIV, achieving excellent antiretroviral medication adherence and overcoming toxicities are no longer the major priorities for his care. For an HIV-uninfected individual similar to Mr H but without weight loss, life expectancy approximates 10 years. Coexisting HIV and weight loss decrease estimated life expectancy. Advanced-stage care is characterized by individualized decisions to defer guideline-driven preventive interventions due to an unfavorable risk-benefit relationship in patients with limited life expectancy. Prognostic information is central to the dialogue with patients when conducting routine screening because many published recommendations are based on long-term benefits. For example, colon cancer screening is no longer recommended when life expectancy is less than 7 years because the harms from screening outweigh potential benefits.68,69
According to a survey completed before widespread use of combination ART, one-half of HIV-positive patients in the United States had not discussed end-of-life preferences with their clinicians.70 A smaller, recent study at an academic clinic showed only 47% of HIV-positive adults aged 45 to 65 years had documented advanced care planning.71 These findings highlight the need for greater attention to end-of-life preference discussions between older-HIV-positive patients and their physicians (Box). The imperative for advanced-care planning is even greater for older HIV-positive patients given their prevalent social isolation and given that advanced care may be provided by governmental and institutional organizations. Prognostic information and patient preferences factor into clinical decision making in cases like Mr H's, in which aggressive testing to evaluate weight loss may have a lower priority than symptom management. Palliative care, a critical factor in the early days of the HIV epidemic, may have an emerging role in improving quality of life for older patients.72,73 Although there are few data on which to make formal recommendations, even when a patient's life expectancy is less than 1 year, continuing antiretroviral medications and opportunistic infection prophylaxis may enhance palliation by minimizing symptoms from HIV-related diseases.72
Mr H and Dr L initially chose a symptom-based approach to evaluating his fatigue and weight loss using focused investigations where benefits outweigh risks. His fatigue and weight loss were investigated by laboratory tests (eg, complete blood cell count, thyrotropin, testosterone); medications were assessed by a pharmacist; and alcohol intake, depressive symptoms, and the quality of his sleep were reviewed by Dr L. A regular exercise program was encouraged, which alone should have been beneficial.74 Rosuvastatin was discontinued and he was switched to a single-tablet antiretroviral regimen (emtricitabine/tenofovir/rilpivirine) to reduce pill burden. Unfortunately the new regimen was associated with increased depressive symptoms and he was switched back to his prior antiretroviral regimen. In follow up, he has remained independent, continues to attend a support group, and has gained 6 lbs, although his fatigue persists.
Whether treating patients in the early, maintenance (chronic care), or advanced stages of care, clinicians should discuss patient preferences and goals, advise patients of available social support, and help determine the most appropriate level of care (eg, assisted living or nursing home). In the advanced-care stage, the priority is to maintain independence and avoid prolonged hospitalizations.
Mr H's success may be attributable to an effective patient-physician alliance and a multidisciplinary approach; however, optimal models of care for older HIV-positive patients are not completely understood. A Cochrane review could not identify sufficient evidence to recommend any single model of care for HIV-positive patients irrespective of age. The reviewers did find that better case management may improve outcomes.75 Published descriptive examples of clinics serving older HIV-positive adults focus on use of multidisciplinary teams and screening for specific complications such as polypharmacy and cognitive impairment.76 Multidisciplinary models, such as the Ryan White Care
Act-affiliated clinics,77 may be beneficial and the integration of geriatric principles will likely be needed in all clinics where there are appreciable numbers of older HIV-positive patients. Internationally, HIV programs must consider the role of chronic diseases when serving an increasing population of older HIV-positive patients.78