HIV and ageing

Susan Herrmann : Institute for Immunology and Infectious Diseases, Murdoch University WA
Matthew Skinner : General/Infectious Diseases Physician, A/Medical Co-Director, Medical Division, Sir Charles Gairdner Hospital, WA

While a cure remains elusive, longevity in the context of human immunodeficiency virus (HIV) infection is attainable for those with access to primary health care and antiretroviral therapy (ART). In Australia, between the years 1996 and 2006 the number of people with HIV infection over the age of 65 years grew tenfold. By 2012 about 10% of new diagnoses were in people aged 50-59, reflecting a global trend of prolonged survival and late acquisition among older adults. However, despite the positive outcomes of effective and tolerable treatments, it is becoming increasingly evident that independent factors related to HIV infection are complicating the ageing process for people living with HIV.

As a matter of definition the Australian Government considers age chronologically and, accordingly, people aged 65 years and older are classified as 'older'. Coupled with this definition is the notion of 'biological' ageing and the general perception of deficit-associated changes even in the absence of identifiable pathology [1] This concept creates a boundary between so-called 'normal' ageing and 'abnormal' ageing[2]. and these boundaries, constructed in a Western context, influence the practice of medicine as it relates to older individuals in society.

Biological ageing per se is characterised by substantial heterogeneity between individuals modified by genetic, epigenetic and psychological factors. It is increasingly recognised that many of the physiological changes and diseases associated with ageing, such as cardiovascular disease and osteoporosis, are modifiable or preventable. However, HIV infection in the absence of a cure, is not inherently modifiable and evidence suggests that HIV infection augments biological ageing directly by way of prolonged immunodeficiency, chronic immune activation and side effects of treatment; and indirectly via anxiety and depression.

In addition to conditions commonly associated with ageing in the general population, HIV-associated immunopathology and the diverse pathways that have led to the HIV seropositive status,[3] such as injecting drug use, sex work and men who have sex with men, represent additional risk factors influencing health in later life. High rates of anxiety and depression, substance use and comorbidities together with cumulative unresolved side effects of earlier therapies, e.g. peripheral neuropathy and lipoatrophy, are additional stressors on physiological and psychological systems, which affect health-related quality of life. Consequently, addressing potentially modifiable stressors is a hallmark of quality HIV care. It is becoming evident that people with HIV infection, especially those with a history of prolonged immunodeficiency, have complex care needs at the end of life.

While HIV management in Australia can be framed within chronic disease models, there is a need to consider HIV-related influences on ageing including taking a 'life course perspective',[4] and to integrate geriatric principles into care that maximises mental and physical function, minimises frailty and directly addresses factors that affect quality of life. Rowe and Kahn proposed deflecting focus from a pathological vs non-pathological definition of ageing by articulating three components of 'successful' ageing: low risk of disease and disease-related disability; maintenance of high mental and physical function; and continued engagement with lifestyle.[5] These components provide a goal-oriented framework for HIV management in older Australians. In this section we will explore some of the issues associated with HIV and ageing and provide guidance for practitioners.

Disease and disease-related disability

Multimorbidity

Major reductions in HIV-associated mortality as a consequence of effective treatment and decreased rates of ageing-related conditions have increased the median life expectancy in adults with HIV infection. However, immunodeficiency and illnesses involving inflammatory processes e.g. cardiovascular, bone, renal and liver disease, cancers and neurocognitive decline are clustering in older people with HIV leading to a geriatric syndrome not usually seen in individuals without HIV until later in life.[6], [7], [8], [9], [10] This syndrome is characterised by multimorbidity, consequent polypharmacy and a condition known as frailty,[11] which threaten function and quality of life. Understanding and managing the stressors leading to age-associated non-communicable comorbidities and identifying people at high risk of disability and frailty are necessary. Disability predicts adverse health outcomes, including falls, and is associated with a lack of education,[12] therefore management requires consideration of the social, cultural, environmental and economic context of the patient and should incorporate preferences and priorities.[13] These considerations will lead to a model of patient-centred and shared care where HIV may not be the major pressing condition. New clinical care frameworks incorporating the principles of geriatric medicine may be needed.

The transition from a state of pre-frailty to frailty has been defined by the presence of three or more criteria: unintentional weight loss of 4.5 kg in the past year; exhaustion; diminished grip strength; slow walking speed; and low physical activity.[14] These factors may all occur earlier in people living with HIV.[15] Research by Rockwood and colleagues  suggests that frailty is a multidimensional construct with medical and psychological antecedents, and it is a condition associated with age and dysregulation of multiple physiological systems.[16] The Australian and New Zealand Society for Geriatric Medicine provides guidance for Comprehensive Geriatric Assessment  in the community noting that persons with moderate amounts of disability benefit most from the process, and that identifying all impairments may mitigate against disability.[17] However, an important element of clinical frailty is loss of skeletal muscle mass, or sarcopenia, which is associated with extrinsic factors like lifestyle, nutrition and comorbidities, all of which feature in HIV disease. In addition, independently of these factors, HIV infection is thought to lead to frailty through the process of chronic immune activation and immune senescence.[18] Immunosenescence is a term referring to the progressive deterioration of innate and adaptive immune responses associated with normal ageing, and it may, at least in part, be associated with the cumulative effects of periods of immune activation across an individual's life span. In HIV, depletion of the CD4+ HIV-specific T cells and viral factors that induce down regulation of the major histocompatibility complex (MHC) Class 1 molecules from the surface of infected cells, interfere with cytotoxic T cell recognition and consequently affect the immune response to infection. In addition, fundamental alterations of T-cell characteristics through persistent activation and differentiation, play a part in HIV-induced immune senescence. These alterations include: loss of coreceptor stimulatory and cytokine secretion capacity; and shortened telomere length which, ultimately, limits T-cell replicative ability.[19] This putative acceleration of deterioration could be responsible for some of the factors and biological ageing associated with HIV, but is not necessarily unique to this condition.

Bone and muscle ageing

The primary objective in healthy adults is to prevent bone loss occurring prematurely and decrease fracture risk later in life. In addition to traditional risk factors, people with HIV infection are at increased risk of bone disease via HIV viraemia, exposure to antiretroviral drugs and smoking and liver disease.[20] Bone disease in HIV infection is characterised by a high bone turnover rate evidenced by elevated markers of bone formation and resorption.[21] Risk of fragility fracture can be assessed by using the Fracture Risk Assessment Tool (FRAX®)[22]  and further informed by dual energy X-ray absorptiometry (DXA) in men over 50 years of age, post-menopausal women, patients with a history of fragility fractures, those on chronic glucocorticoid treatment or with a high risk of falls.

Interventions to preserve normal gait and balance and increase muscle strength should be given the same priority as addressing cardiovascular risk factors.[23] Adjustments may need to be made to antiretroviral regimens since some drugs are more bone-sparing than others. Particular attention should be given to establishing baseline risk in people newly diagnosed who are over the age of 50 years since this may affect choice of first-line ART.[24]

In older adults (over 50 years) prevention and treatment of osteoporosis to minimise risk of fragility fractures is the focus of management. Attention should be paid to advising that the recommended daily intake (RDI) for calcium be understood, and that adequate vitamin D levels are maintained. If unable to be maintained, then vitamin D must be supplemented. The National Health and Medical Research Council (NHMRC) recommends the following targets for calcium intake per day:

• Ages 51-70 years: women 1300 mg; men 1000 mg
• Over 70 years: women 1300 mg; men 1300 mg

The preferred source of calcium is dietary. Australians are most likely to consume calcium from dairy products and an intake of 1300 mg/day or three serves should suffice (Australian National Nutrition Survey). However, in older persons and individuals with osteopenia and osteoporosis, at least one serve should be fortified. Therefore, supplements of oral calcium at doses of 500 mg-600 mg/day in people whose dietary intake is not sufficient or who have low bone density, are recommended. This recommendation needs to be balanced against the risks associated with excess calcium such as coronary artery calcification and increased myocardial infarction risk.[25]

Vitamin D (hydroxy-vitamin D or 25(OH)D or cholecalciferol) can be obtained from the diet, supplements or synthesised in the skin during sun exposure (limited by melatonin skin pigment). Together with parathyroid hormone, vitamin D preferences homeostasis of calcium levels in the blood over skeletal stores thus maintaining blood levels through bone resorption. The recommended level of 25(OH)D is more than 50 nmol/L (end of winter), more than 60 nmol/L (end of summer) for older adults. However the dietary intake  of most Australians is not adequate to meet that requirement. Elderly people are further compromised since the capacity to synthesise vitamin D in the skin is diminished, as is frequency of sun exposure, especially in nursing home residents. Dark skin, obesity, chronic kidney disease, malabsorption and treatment with efavirenz-containing regimens are also risk factors for low vitamin D levels.[26] For people over 50 years of age, vitamin D plus calcium supplementation appears beneficial in reducing rates of fracture but in people with a history of fracture, treatment with drugs that reduce bone resorption is recommended.[27],[28]

Exercise especially that which is bone loading, can be beneficial to increase bone mineral density in older adults, however with increasing age, muscle loading becomes increasingly relevant in order to avoid sarcopenia and improve strength and coordination. Loss of height can cue that subclinical vertebral fractures have occurred and further assessment by DXA and radiography is indicated.[29] Supervised exercise programs for patients with advanced osteoporosis can help avoid further fractures, prevent falls and reduce declines in quality of life. Such programs for older adults should focus on posture and balance, gait and coordination; and hip and trunk stabilisation.[30] Specific directed therapies for osteoporosis should be considered when appropriate, with consideration of primary or secondary causes. Expert assistance from an endocrinologist, or other appropriate specialist, may be necessary

Age-related considerations

Encourage physical activity, discourage sedentary behaviour
Encourage activities that will maintain or improve strength and balance congruent with patients' bone health
Measure and record height every 1 – 2 years
Follow current recommendations for evaluation and management of bone disease in HIV
Establish risk of fracture by utilising the FRAX® score
Measure bone density annually using DEXA scanning in men over 50 years, post-menopausal women, patients with a history of fragility fractures, those on chronic glucocorticoid treatment or with a high risk of falls
Optimise  calcium  and vitamin D levels in line with NHMRC guidelines and consider regular screening of calcium, phosphate and 25(OH)D
Consider dietary supplements like vitamin D to maintain recommended levels
Consider avoiding tenofovir in people with osteoporosis when initiating antiretroviral therapy and consider risk for switch agents (tenofovir vs abacavir).

Renal function and ageing

The ageing of the population with HIV infection has important implications for renal disease within this patient group. The risk of kidney disease increases with age and is linked to adverse long-term outcomes.  As well, older patients are at increased risk for multiple drug prescribing (polypharmacy) and medication-related toxicity.

Older age confers an increased risk of chronic kidney disease (CKD) as a result of increasing comorbidity and a physiological decline in renal function with age.  Renal risk factors associated with CKD in the elderly include hypertension, diabetes, obesity, cardiovascular disease, smoking and nephrotoxic medications. More frequent monitoring is warranted.[31] Kidney function can be simply assessed by plasma creatinine concentration which informs the calculation of the estimated glomerular filtration rate (eGFR). The combination of a patient's eGFR and an assessment for the presence of albuminuria, as well as a clinical assessment of a patient's renal risk factors identifies patients at greatest risk of progression to CKD. Changes in body composition such as low-muscle mass and total body water can confound estimates of age-related decreases in GFR, which is generally about 1% per year after the age of 35. The increase in blood pressure seen in ageing is also associated with rate of renal decline, with issues such as diabetic nephropathy resulting in proteinuria and subsequent renal damage.[32] Both hypertension and diabetes are common comorbidities in older people with HIV and intensive screening and risk factor modification are indicated. Blood pressure control is important, and the antiproteinuric antihypertensives, angiotensin inhibitors or ACE inhibitors, are recommended as first-line treatment.

Antiretroviral drugs may also be implicated in renal impairment (see section on renal disorders). Tenofovir can accumulate in the proximal tubule and its usage must be accompanied by careful monitoring of eGFR, serum phosphate and urinary protein/creatinine excretion. Other drugs, such as atazanavir and indinavir, can cause crystals increasing the risk of nephrolithiasis. Individually, many drugs have potential for renal damage and the cumulative effects of multiple agents often see in people with long-term HIV infection should be considered. Polypharmacy in these patients is also an important consideration.  Renal surveillance and active screening for risk factors with stringent management are important to ensure optimal renal function in elderly patients.

Age-related considerations

Provide patient education regarding the benefits of life-style changes to benefit kidney health specifically, weight loss and smoking cessation
Be pharmacovigilant. Avoid nephrotoxicity in elderly people, with avoidance of polypharmacy wherever possible
Avoid nephrotoxic medication
Assess the patient's renal risk factors, including assessment for renal impairment at baseline. Consider the patient's clinical risk factors and measure his or her blood pressure
Screen at baseline for renal disease (EUC and uACR), with at least 12-monthly screening for eGFR
Test 6-12 monthly urinary protein/creatinine ratio and serum phosphate, if on tenofovir
Assess cardiovascular risk (lipids, blood pressure, smoking, diabetes)
Refer to a nephrologist if decline in eGFR, unexplained proteinuria or concerns of antiretroviral-related nephrotoxicity.

Liver function and ageing

Liver disease is a leading cause of death in people who are HIV seropositive.  Older people in general are more likely to present with severe or chronic liver disease related to age-related declines in liver volume and blood flow. This can result in reduced clearance of drugs and can increase the prevalence of drug-induced injury. In particular, antiretroviral agents such as nevirapine, tipranavir, high dose ritonavir and zidovudine are potentially hepatotoxic. People with HIV are also vulnerable to liver injury through persistent HIV replication, diabetes mellitus, substance use, particularly alcohol and nicotine, and untreated hepatitis C (HCV) virus infection, rates of which are higher than in individuals without HIV.[33],[34]

For people with HCV co-infection, older age and duration of HCV infection over 20 years are risk factors for the development of cirrhosis. Elderly adults also progress to cirrhosis more quickly but a higher prevalence of comorbid conditions may limit their eligibility to direct-acting antivirals (DAAs). In addition age-related changes to liver and renal function result in more frequent dose adjustments and higher dropout rates from treatment programs. While the DAAs are well tolerated, with marked improvement in efficacy against HCV even in co-infection with HIV, they are relatively new with longer-term issues unknown at this stage.[35] It is important to consider the detrimental lifetime effects of more common genetic conditions that may result in chronic iron overload.  Routine monitoring of liver function at clinic visits is helpful to foreshadow potential issues. In patients with current liver disease and a history of active HCV or hepatitis B virus (HBV) infection, monitoring for cirrhosis and hepatocellular carcinoma is necessary.

Age-related considerations

Screen liver function (biochemistry) 6 monthly
Update hepatitis A virus, HBV and HCV infection status annually, including assessment of the risk of sexual transmission of HCV
Screen for cirrhosis by ultrasound/fibroscan
Undergo gastroscopy if cirrhosis present and preventive measures (beta-blockers if varices present and lactulose therapy to prevent encephalopathy)
Subject to surveillance for hepatocellular carcinoma (ultrasound annually and alfa-feto protein 6 monthly).

Sexual function and sexuality

People with HIV infection can be expected to experience the usual age-related milestones but can face additional challenges with regard to sexual function and sexuality. In terms of sexual function, sex hormone levels, responsible for libido and secondary sexual characteristics, decline with age: testosterone drops from peak levels at age 30 by about 1% per annum; and, oestrogen falls more precipitously in the perimenopausal period.[36] These changes may vary greatly between individuals, and within individuals and can impact sexual function, sexual identity and relationships. Males can expect a decline in erectile function, with early manifestations represented by less nocturnal tumescence. This can affect turgidity and duration of erections, delay arousal and orgasms, potentially creating psychological tensions, which exacerbate the physiological functions. Erectile dysfunction may be amenable to specific therapy, but other medications can jeopardise performance, enjoyment or have limited impact on underlying problems. Females may experience vaginal dryness, delays in arousal and dyspareunia in the extreme. Libido is primarily driven via testosterone, which will decline with advancing age.[37]

HIV infection complicates intimate relationships and can create barriers to sexual fulfilment, including self-imposed abstinence driven by a fear of transmitting the infection.[38] Psychological concerns, including fear of transmission, have been shown to be related to stigma[39] and can cause grief and distress within existing relationships and present barriers to the establishment of new relationships in both men and women. This situation arises despite the reconceptualisation of HIV as a chronic vs fatal illness.[40],[41] These concerns are associated with a diminution in quality of life and may not be addressed in the clinical consultation. Psychologically targeted intervention may be helpful and should be pursued in consultation with the patient.[42]

Ongoing sexual activity should be reviewed in the context of infection risk, transmission potential (HIV, HCV, HBV, other sexually-transmitted infections [STIs]), new STIs, the presence of other chronic health conditions [43], [44], [45] and perceptions of wellbeing. Notably, psychological wellbeing appears associated with protected sex behaviour.[46] Screening for STIs should continue at recommended intervals suggested by various guidelines; and patients should be counselled in relation to risk behaviour. However, sexual health includes the totality of the human experience. A pragmatic approach to questions concerning libido, intimacy loss or absence of sexual interest may uncover dysfunction amenable to intervention. Should sexual dysfunction or concern be divulged, physiological (endocrine, cardiovascular) and psychological assessment, with attendant referral or treatment, can be embarked on.

Recommendations

Screen annually for sexual risk (direct questioning), test for STIs based upon risk exposure
Review patient desires regarding sex, intimacy and sexuality
Consider the contribution of psychosocial and pharmacological factors, as well as comorbidities to sexual dysfunction and barriers to intimacy
Treat/manage specific problems such as erectile dysfunction and dyspareunia.

Pharmacotherapy

Cohort studies have shown that people with  HIV infection  commonly receive medications for dyslipidaemia, disordered glucose metabolism, gastrointestinal symptoms, reduced bone density, hypogonadism, hypertension and depression and that pre-existing metabolic conditions may be exacerbated by the metabolic side effects  of ART.[47] Polypharmacy in the context of HIV can be succinctly described as the concurrent use of six or more medications;[48] and older individuals with HIV infection usually have no difficulty meeting this definition.38 Negative consequences arising from polypharmacy are compounded in elderly people and include an increased risk of falls, drug-drug interactions (DDIs), adverse drug events, risk of toxicity and poor adherence. These consequences translate into increased clinic and hospital visits as well as emergency admissions. Combination treatment for HIV brings a potential for drug-drug interactions (note: see Table  in section Drug interactions for common interactions. See website: http://www.hiv-druginteractions.org/) and most commonly when three or more antiretroviral agents are used, or include a protease inhibitor (PI).[49] Ritonavir, a commonly used PI, inhibits cytochrome P450 3A (CYP3 A) and inhibits the metabolism of other PIs thus boosting their efficacy. However, this inhibition may result in increased blood levels of concomitant medication and toxicity. Conversely non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as nevirapine, efavirenz, etravirine and older PIs such as lopinavir and tipranavir induce CYP3A and coadministration with other medication can result in blood levels which are subtherapeutic. [50] In the context of HIV, loss of antiretroviral potency can lead to viral rebound and drug resistance.

While pill burden and regimen complexity increase the risk of DDIs at any age, older adults with HIV are more susceptible than young people since age-related physiological changes can affect the pharmacodynamic and kinetic properties of medications. Body composition changes associated with ageing, which include initially a gradual replacement of lean muscle for fat and later weight loss associated with frailty and concomitant alterations in total body water, can reduce clearance and prolong the half-life of some drugs. This contributes to increases in drug toxicities and drug interactions seen in very old adults. Legacy effects of early regimens introduced in the mid-1990s e.g. effects of thymidine analogues, and some PIs, have affected many people with HIV infection of long duration and resulted in lipoatrophy, upper body fat accumulation and dysregulated glucose metabolism, respectively. These morphologic changes can complicate pharmacological management and measurement of body fat composition may be useful. In addition, neurocognitive decline, increasing comorbidity, lack of social support and nutritional factors can interact with ageing and affect adherence and persistence with medication.[51]

There is a need for more targeted research into aspects of ART that may be relevant to elderly people including whether monotherapy may be sufficient, boosting is required and whether ART should be stopped at the end of life. The last question will need to address the implications of HIV viraemia and increased infectiousness.

Recommendations

Prescribe conservatively appropriate to the age and life goals of the patient
Assess weight each visit; note gradual changes and unexplained weight loss
Consider body composition and fat assessment
Encourage healthy weight range – more calories may be needed for elderly patients
Obtain a complete medication history
Review medication each visit; include supplements and recreational drugs
Promote health literacy e.g. patients should understand the concept of a fixed dose combination – that it is a composite of a number of drugs; check patient can read the label
Encourage the patient to maintain a list of his or her current medication including doses and schedules
Explore pill taking attitudes (motivated? effective? side effects?)
Encourage reminder devices and calendar pill boxes
Be aware of expense – is the patient failing to fill a script because of expense or only taking the drug intermittently?
Trial non-drug strategies before prescribing, where appropriate, e.g. weight loss; diet/exercise; psychological interventions
Titrate dosing in patient where pharmacodynamics or pharmacokinetic sensitivity may be an issue
Avoid combinations that have known synergistic effects
Ensure efficient communication between providers – electronic records integrated appropriately
Encourage the patient to use the same pharmacy each time
Return unused medications to pharmacy to reduce confusion and promote safe disposal.

Mental health and psychosocial functioning

Physical, mental and psychosocial factors associated with HIV infection have shaped the lives of people affected. Episodic illness and treatment, anxiety and depression and threats to psychological wellbeing presented by HIV-related stigma have resulted in diminished health-related quality of life.  However, improved treatment, lifestyle and psychosocial interventions can mitigate detrimental impacts of HIV infection and increase the possibility for improved coping, optimism and social support.[52],[53] Inherent resilience to stressful circumstances can also buffer negative HIV-related psychosocial pressure.

Subclinical mood and anxiety disorders are common in people with HIV infection as is susceptibility to HIV-associated neurocognitive disorder (HAND), major depression, dysthymia, generalised anxiety disorder and panic attacks. As life expectancy increases, the impact of ageing effects on the brain and psychosocial changes associated with ageing per se are likely to present further challenges.   Although rates of reported depression vary between studies, mood disorders are common in men and women, although men appear to have fewer positive relationships, which may affect their capacity to maintain and develop supportive networks.

Over the course of a life the number of negative life events increases the likelihood of anxiety and perceived stress. In addition, membership of more than one group accorded minority status e.g. gay, disabled, non-English speaking, increases the mental health burden since people must negotiate multiple stigmas including the potential for discrimination from within their own minorities. However, minority burden can be mitigated by emotional and informational support that increases the capacity to cope which, in turn, has a positive effect on psychosocial wellbeing.[54]

Episodic illness and treatment-related side effects of early highly active antiretroviral therapy (HAART) compromised the employment opportunities and finances for a generation of people with HIV. Neurocognitive impairment may necessitate early retirement and limit employment or even volunteering opportunities. Lack of employment and meaningful work can negatively affect social engagement and self-worth leading to reduced psychological health. Straitened financial circumstances can increase stress, anxiety and depression and lead to reduced opportunity to engage in health-seeking behaviours taken for granted by many Australians.

A common concern for people with HIV is uncertainty about the future and ageing in the context of HIV. Will they receive quality aged care? What will they be able to afford? Will they be more vulnerable to stigma and discrimination that they may have experienced in the past, by virtue of frailty? Will they need to negotiate disclosure in a potentially unsupportive setting?

Supportive social ties have been shown to enhance physical functioning and mental health in older adults and stressful social ties are recognised as detrimental.[55] Social support networks are dynamic and shaped by need and circumstance over the life course.[56] These networks are recognised as an important adjunct of successful HIV care, particularly supporting medication adherence; psychological wellbeing and mental health; positive states of mind; coping with the stress of disease and quality of life. Assessing risk of those characteristics that may increase vulnerability to social isolation is an important aspect of HIV management. Some studies have found that older adults have lower levels of social functioning, and report that emotional support is inadequate to their needs. In addition, older adults who find barriers to accessing services have reported more depressive symptoms. 

Sexual orientation influences relationships with families and many gay and lesbian adults have formed families of choice and may have similar social network capacity as individuals without infection. This may not be true across cultures however, and research by Emlet showed that people of colour had lower scores on the subscales of the Lubben Social Network scale for friends, confidants and instrumental support.[57],[58],[59] These data highlight the cultural nuances of stigma concerns.

Age-related considerations

Assess risk of social isolation (age, gender, sexual orientation, ethnicity, poverty, unemployment, family and friendship ties)
Strengthen social assistance packages incrementally and appropriately
Screen regularly for depression and anxiety
Consider quality of life issues that might impact on psychosocial functioning e.g. financial concerns
Appreciate understanding of the patient's life course and the sociopolitical context of HIV
Identify triggers influencing psychosocial functioning e.g. significant life events: loss of relationship, death in the family, job loss or change.
Help people manage HIV disclosure and understand their rights (aged-care accommodation)
Consider cognitive and behavioural interventions to improve function and remove triggers to dysfunction
Target modifiable factors to increase opportunities for social interaction
Encourage people to find meaningful activity e.g. volunteering.

Neurocognitive function and ageing

Despite high rates of viral suppression, older people treated long term with ART are complaining of memory problems, slowness and difficulty multitasking, planning and concentrating. Between 15 and 50% of people living with HIV are purported to experience neurocognitive impairment, but, in people with access to currently used ART regimens, severe forms of neurocognitive impairment are uncommon.[60] Cognitive impairment, which may be episodic and go unnoticed, can also occur in cardiovascular disease, metabolic, co-infection and sleep and mood disorders independently of HIV infection. Cultural and demographic factors can confound efforts to tease out HIV-related impaired cognition. However, the contribution of HIV is thought to be via a history of compromised immunity and ongoing immune activation.[61], [62], [63] Despite increasing research interest, neurocognitive function is not measured commonly in HIV clinical practice and in the context of longevity, the relevance of doing so is becoming apparent.

Maintaining cognitive function is necessary to health and quality of life. In the context of HIV, the effects of impaired functioning are pervasive. Most obviously, there are implications for medication adherence and safe dosing.[64],[65] Impaired neurofunctioning may impact on mood and behaviour affecting employment, driving capacity and interpersonal relationships.

Clinically, a dominantly subcortical presentation with deficits in mental slowness, attention and memory and impaired executive functioning has been observed as well as extra pyramidal features.[66], [67], [68] However in mild cases these distinguishing features may not be clear. There is some clinical overlap with Alzheimer disease but studies imply different pathogenic pathways. Vascular cognitive impairment can mimic HAND clinically and as shown by magnetic resonance imaging (MRI) brain scan changes. MRI spectroscopy of the brain can be helpful but in mild cases it too can be less definitive than desired. The following domains should be particularly assessed by a neuropsychologist: speed of information processing, attention, working memory, memory and verbal/language, sensory-perceptual and motor skills.[69]

Attributing cognitive impairment to HIV infection may be difficult since impairment may go undetected, and be confounded by other factors; such as the ageing process, educational level, substance use, mood disorders and comorbidities. The neuropenetrance capacity of antiretroviral drugs is a consideration in choice of treatment since the virus crosses the blood brain barrier during acute infection and can establish latency even under effective treatment conditions. Uncertainty around the contribution of antiretroviral drugs to the risk of developing HIV-related cognitive impairment prevails.[70]

Guidelines that promote standard of care for persons living with HIV infection recommend assessing neurocognitive functioning.[71],[72] A diagrammatic clinical decision-making pathway is provided to assist practitioners choose management strategies on the basis of the responses.[73] If this brief test is abnormal, the patient should be referred for comprehensive assessment. Neuropsychological assessment is recommended early; however it is often not possible because of limited resources. A more appropriate step is neurological evaluation either by a physician with neurology expertise or a neurologist.[74] Findings may indicate the need for further investigation by neuropsychological testing, neuroimaging or examination of cerebrospinal fluid.   In the clinical setting it is recommended that patients be engaged in conversations about their ability to manage their medication, and  daily home and work activities, since deteriorating quality of life may be the earliest indication that something is amiss.

Screening can be justified in the context of slowing the ageing process by addressing modifiable risks, promoting health-seeking behaviours, including exercise and social engagment, and by taking a biopsychosocial perspective of HIV care.

Age-related considerations

Establish baseline neurocognitive function in order to track changes over time
Consider cultural and demographic factors that might influence findings
Assess depression, anxiety  or other comorbidities that may imapct neurocognitive function
Refer for psychology or psychiatric assessment if dementia is suspected
Follow recommended guidelines[75]
Assess medication adherence and pill taking behaviour at every visit
Be alert to changes in health-related quality of life
Review antiretroviral therapy  with a consideration of the neuropenetrance capacity of the regimen
Arrange geriatric assessment to access support and services.

 

Caring for the aged in culturally and linguistically diverse communities

Bernadette Wright : Department of Health WA
Aesen Thambiran : Department of Health WA

For elderly people from culturally and linguistically diverse (CALD) backgrounds who have migrated to or sought refuge in Australia, culture and language may increasingly present as significant barriers to seeking appropriate and timely assistance. Despite the campaign to significantly destigmatise HIV among mainstream Australian society, the notion of HIV is still heavily stigma-loaded in non-Western cultures. Culture-based beliefs or myths about HIV – most of which lack scientific basis – are likely to play a key role perpetuating the stigma that will prevent those with HIV infection from disclosing their HIV infection. The lack of health literacy among elderly people from an ethnic background will also contribute to low rates of self-reporting of symptoms associated with HIV and thus, timely intervention. Owing to cultural beliefs, elderly people and their families may attribute symptoms to signs of ageing and not seek medical consultation – particularly in the early stages of the infection. There is also a likelihood of a misdiagnosis or missed diagnosis in any given transcultural consultation due to the cultural idioms of distress that may affect presentation or hinder receptiveness to treatment options.  For elderly people from an ethnic background, the prospect of communicating distress using concepts that are widely understood and familiar in Australian culture, and in a language that is not their mother tongue, are factors that exacerbate the help-seeking difficulties because bilingual migrants tend to revert to their mother tongue as they grow older. Sociocultural factors other than language or the experience of shame and stigma within the community may also influence help-seeking. Lack of awareness of services, pathways to these services, previous negative experience with health-care services and the fear that the service will not be culturally responsive or sensitive will all deter service utilisation by CALD elderly people. Those who have no traditional sources of support may, upon accessing services, need to be linked with advocates in whom they can trust and confide in order that their needs and any problems arising with the complexities of their medication regimen are accurately and promptly conveyed to the treating clinician.

Age-related considerations

Try to understand the meaning of HIV within the given culture – particularly the cultural beliefs about HIV and how it should be treated.
Use the services of an accredited interpreter to communicate and engage with elderly people from an ethnic background
Validate cognitive tests and inventories to be used in the culture of the client.
If using questionnaires, arrange a pre-test briefing with the interpreter to ensure that the interpreter understands the reason for the test, and how to administer the test appropriately.
Use bilingual clinicians who speak the language of the client
Ensure that printed material is in the client's own language if the client does not have family members (primarily, second generation) who are familiar with any concept reflected in the documents, and can explain this to the elderly client in his or her own language.
Be prepared that stigma can hinder openness in communication –approaching sensitive issues may take more than one encounter.

Engagement with life: end-of-life and palliative care issues

End of life planning is important and relevant for all people. Planning and advance directives have been shown to improve care for patients and psychosocial outcomes in surviving relatives; and doctors are responsive to training opportunities.[76],[77]  HIV infection can complicate care at the end of life but past research in other contexts has indicated that people with HIV infection were less likely to discuss advanced care directives than others with serious illness.[78],[79]

A focus on quality of life as a key component of HIV management at all ages should facilitate discussion and empower patients to be clear about their wishes.[80] Formal advanced care directives would be a natural extension of an ongoing conversation with the patient concerning their priorities. The continuity of HIV care in many Australian health settings will underpin this approach. And in a multicultural context advanced care planning proved to be equally as acceptable in non-English speaking people in comparison with those with English speaking backgrounds, although this was not in the context of HIV care.[81]  More research is clearly indicated.

Antiretroviral therapy reduces HIV viral load thereby preventing immune decline and death from acquired immune deficiency syndrome (AIDS).  However, as people with HIV approach the end of life and face dying of some other cause, the potential benefits of antiretroviral therapy could be reconsidered. While there is much research concerning when to start antiretroviral therapy there has been less attention paid to the end-of-life planning in general and the implications for continuing antiretroviral therapy, in particular. The clinical benefits of antiretroviral therapy can be summarised as:

  • Preventing opportunistic infections
  • Preventing non-AIDS events related to ongoing immune activation
  • Preventing constitutional symptoms e.g. fatigue, weight loss
  • Delaying the progression of AIDS.

These benefits could be reconsidered at the end of life, however the impact of discontinuing antiretroviral therapy at this stage has not been well researched. Stopping treatment for HIV is likely to be a significant step for individuals and their families, equally as relevant as discontinuing treatment for cancer when hope for cure or palliation is lost. Patients who experience negative side effects of antiretroviral therapy, who find that it interacts with other medication, or contributes to pill burden, may favour discontinuation to improve quality of life.  If antiretroviral therapy is ceased, viral rebound could indirectly lead to discrimination when high intensity care is required.

The decision to stop antiretroviral therapy needs to be carefully considered in the context of the person's palliative care plan weighing the benefits and disadvantages to the individual.

Recommendations

Adopt a patient–centred approach to management
Foster ongoing discussion concerning quality of life
Promote health literacy early, e.g. practices that promote continuity of care
Discuss advanced care directives or planning – ensures wishes are met and reduces distress for families
Identify people early in the disease trajectory who might benefit from palliative care services
Increase support incrementally.
1.
Rowe JW, Kahn RL. Human aging: Usual and successful. Science 1987;237:143-9. 
2.
O'Rourke HM, Ceci C. Reexamining the boundaries of the 'normal' in ageing. Nurs Inq 2013;20:51-9. 
3.
Sankar A, Nevedal A, Neufeld S, et al. What do we know about older adults and HIV? A review of social and behavioral literature. AIDS Care 2011;23:1187-207. 
4.
Rosenfeld D, Bartlam B, Smith RD. Out of the closet and into the trenches: Gay male Baby Boomers, aging, and HIV/AIDS. Gerontologist 2012;52:255-64. 
5.
Rowe JW, Kahn RL. Human aging: Usual and successful. Science 1987;237:143-9. 
6.
Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011;53:1120-6. 
7.
Hasse B, Ledergerber B, Furrer H, et al. Morbidity and aging in HIV-infected persons: The Swiss HIV Cohort Study. Clin Infect Dis 2011;53:1130-9. 
8.
Pathai S, Bajillan H, Landay AL, et al. Is HIV a model of accelerated or accentuated aging? J Gerontol 2014;69:833-42. 
9.
Schouten J, Wit FW, Stolte IG, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: The age HIV cohort study. Clin Infect Dis 2014;59:1787-97. 
10.
Kooij KW, Wit FWNM, Schouten J, et al. HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. AIDS 2016;30:241-50. 
11.
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-56. 
12.
Avila-Funes JA, Pina-Escudero SD, Aguilar-Navarro S. Cognitive impairment and low physical activity are the components of frailty more strongly associated with disability. J Nutr Health Aging 2011;15:683. 
13.
Boyd CM, Lucas GM. Patient-centered care for people living with multimorbidity. Curr Opin HIV AIDS 2014;9:419-27. 
14.
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-56.{ref}Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-56. 
15.
Kooij KW, Wit FWNM, Schouten J, et al. HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. AIDS 2016;30:241-50. 
16.
Rockwood K, Stolee P, McDowell I. Factors associated with institutionalization of older people in Canada: Testing a multifactorial definition of frailty. J Am Geriatr Soc 1996;44:578-82. 
17.
Jamieson G, Penhall R. Position Statement No. 8. Comprehensive Geriatric Assessment and Community Practice. Australas J Ageing 200;19:165–71. 
18.
Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci 2007;62:1279-86. 
19.
Appay V, Almeida JR, Sauce D, et al. Accelerated immune senescence and HIV-1 infection. Exp Gerontol 2007;42:432-7. 
20.
Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and managment of bone disease in HIV. Clin Infect Dis 2015;60:1242-51. 
21.
Mallon PWG. Aging with HIV: osteoporosis and fractures. Curr Opin HIV AIDS 2014;9:428-35. 
22.
FRAX® WHO Fracture Risk Assessment Tool [internet]. Available at: https://www.shef.ac.uk/FRAX/tool.jsp (last accessed 12 February 2016). 
23.
Ebeling PR, Daly RM, Kerr DA, et al. Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia. Med J Aust 2013;199:S1. 
24.
Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and managment of bone disease in HIV. Clin Infect Dis 2015;60:1242-51. 
25.
Ebeling PR, Daly RM, Kerr DA, et al. Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia. Med J Aust 2013;199:S1. 
26.
Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and managment of bone disease in HIV. Clin Infect Dis 2015;60:1242-51. 
27.
Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and managment of bone disease in HIV. Clin Infect Dis 2015;60:1242-51. 
28.
Ebeling PR, Daly RM, Kerr DA, et al. Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia. Med J Aust 2013;199:S1. 
29.
Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and managment of bone disease in HIV. Clin Infect Dis 2015;60:1242-51. 
30.
Ebeling PR, Daly RM, Kerr DA, et al. Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia. Med J Aust 2013;199:S1. 
31.
Yombi JC, Jones R, Pozniak A, et al. Monitoring of kidney function in HIV-positive patients. HIV Med 2015;16:457-67. 
32.
Harris K. Progression of chronic renal disease. In: Renal Disease Prevention and Treatment 1998. 
33.
Mohr R, Schierwagen R, Schwarze-Zander C, , et al. Liver fibrosis in HIV patients receiving a modern cART: Which factors play a role? Medicine (Baltimore) 2015;94:e2127. 
34.
Rockstroh JK, Mohr R, Behrens G, et al. Liver fibrosis in HIV: Which role does HIV itself, long-term drug toxicities and metabolic changes play? Curr Opin HIV AIDS 2014;9:365-70. 
35.
Thompson AJ. Australian recommendations for the management of hepatitis C virus infection: a consensus statement. Med J Aust 2016;204:268-72. 
36.
Conde DM, Silva ET, Amaral WN, et al. HIV, reproductive aging, and health implications in women: a literature review. Menopause 2009;16:199-213. 
37.
Russell DB. Sexual function and dysfunction in older HIV-positive individuals. Sex Health 2011;8:502-7. 
38.
Siegel K, Schrimshaw EW. Reasons for the adoption of celibacy among older men and women living with HIV/AIDS. J Sex Res 2003;40:189-200. 
39.
Herrmann S, McKinnon E, Hyland NB, et al. HIV-related stigma and physical symptoms have a persistent influence on health-related quality of life in Australians with HIV infection. Health Qual Life Outcomes 2013;11:56. 
40.
Siegel K, Lekas HM, Schrimshaw EW. Serostatus disclosure to sexual partners by HIV-infected women before and after the advent of HAART. Women Health 2005;41:63-85. 
41.
Siegel K, Schrimshaw EW, Lekas HM. Diminished sexual activity, interest, and feelings of attractiveness among HIV-infected women in two eras of the AIDS epidemic. Arch Sex Behav 2006;35:437-49. 
42.
Psaros C, Barinas J, Robbins GK, et al. Intimacy and sexual decision making: Exploring the perspective of HIV positive women over 50. AIDS Patient Care STDs 2012;26:755-60. 
43.
Basson R, Weijmar Schultz W. Sexual sequelae of general medical disorders. Lancet 2007;369:409-24. 
44.
Lindau ST, Schumm LP, Laumann EO, et al. A study of sexuality and health among older adults in the United States. N Engl J Med 2007;357:762-74. 
45.
Wilson TE, Jean-Louis G, Schwartz R, et al. HIV infection and women's sexual functioning. J Acquir Immune Defic Syndr 2010;54:360-7. 
46.
Golub SA, Botsko M, Gamarel KE, et al. Dimensions of psychological well-being predict consistent condom use among older adults living with HIV. Ageing Int 2013;38:179-94. 
47.
Schouten J, Wit FW, Stolte IG, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: The age HIV cohort study. Clin Infect Dis 2014;59:1787-97. 
48.
Gleason LJ, Luque AE, Shah K. Polypharmacy in the HIV-infected older adult population. Clin interv Aging 2013;8:749-63. 
49.
Gleason LJ, Luque AE, Shah K. Polypharmacy in the HIV-infected older adult population. Clin interv Aging 2013;8:749-63. 
50.
Gleason LJ, Luque AE, Shah K. Polypharmacy in the HIV-infected older adult population. Clin interv Aging 2013;8:749-63. 
51.
So-Armah K, Freiberg MS. Cardiovascular disease risk in an aging HIV population: not just a question of biology. Curr Opin HIV AIDS 2014;9:346-54. 
52.
Rueda S, Law S, Rourke SB. Psychosocial, mental health, and behavioral issues of aging with HIV. Curr Opin HIV AIDS 2014;9:325-31. 
53.
Lyons A, Pitts M, Grierson J. Growing old as a gay man: psychosocial well-being of a sexual minority. Res Aging 2013;35:275-95. 
54.
Lyons A, Pitts M, Grierson J. Growing old as a gay man: psychosocial well-being of a sexual minority. Res Aging 2013;35:275-95. 
55.
Lubben J, Blozik E, Gillmann G, et al. Performance of an abbreviated version of the Lubben Social Network Scale among three European community-dwelling older adult populations. Gerontologist 2006;46:503-13. 
56.
Antonucci TC, Ajrouch KJ, Birditt KS. The Convoy Model: explaining social relations from a multidisciplinary perspective. Gerontologist 2014;54:82-92. 
57.
Lubben J, Blozik E, Gillmann G, et al. Performance of an abbreviated version of the Lubben Social Network Scale among three European community-dwelling older adult populations. Gerontologist 2006;46:503-13. 
58.
Emlet CA. An examination of the social networks and social isolation in older and younger adults living with HIV/AIDS. Health Soc Work 2006;31:299-308. 
59.
Emlet CA. Current knowledge and future directions on aging and HIV research. Behav Med 2014;40:143-8. 
60.
Mind Exchange Working Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the Mind Exchange Program. Clin Infect Dis 2013;56:1004-17. 
61.
Ellis RJ, Badiee J, Vaida F, et al. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 2011;25:1747-51. 
62.
Muñoz-Moreno JA, Fumaz CR, Ferrer MJet al. Nadir CD4 cell count predicts neurocognitive impairment in HIV-infected patients. AIDS Res Hum Retroviruses 2008;24:1301-7. 
63.
Valcour V, Yee P, Williams AE, et al. Lowest ever CD4 lymphocyte count (CD4 nadir) as a predictor of current cognitive and neurological status in human immunodeficiency virus type 1 infection - The Hawaii aging with HIV cohort. J Neurovirol 2006;12:387-91. 
64.
Barclay TR, Hinkin CH, Castellon SA, et al. Age-associated predictors of medication adherence in HIV-positive adults: Health beliefs, self-efficacy, and neurocognitive status. Health Psychol 2007;26:40-9. 
65.
Woods SP, Dawson MS, Weber E, et al. Timing is everything: antiretroviral nonadherence is associated with impairment in time-based prospective memory. J Int Neuropsychol Soc 2009;15:42-52. 
66.
Heaton RK, Marcotte TD, Rivera Mindt M, et al. The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc 2004;10:317-31. 
67.
Woods SP, Moore DJ, Weber E, et al. Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 2009;19:152-68. 
68.
Brew BJ, Chan P. Update on HIV dementia and HIV-associated neurocognitive disorders. Curr Neurol Neurosci Rep 2014;14:468. 
69.
European AIDS Clinical Society (EACS). Guidelines. Version 8.0. October 2015. Available at: http://www.eacsociety.org/files/guidelines_8_0-english_web.pdf (last accessed 20 May 2016). 
70.
Underwood J, Robertson KR, Winston A. Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease? AIDS 2015;29:253-61.{ref},{ref}Caniglia EC, Cain LE, Justice A, et al. Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions. Neurology 2014;83:134-41. 
71.
Mind Exchange Working Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the Mind Exchange Program. Clin Infect Dis 2013;56:1004-17. 
72.
55 People aged over 45 years, patients with prior central nervous system (CNS) disorders or infections, and those with cardiovascular disease or cardiovascular disease risk factors are considered at higher risk. Three questions derived from the HIV Dementia Scale are posed to patients and their responses scored.{ref}Power C, Selnes O, Grim J, et al. HIV Dementai Scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovirol 1995;8:273-8. 
73.
European AIDS Clinical Society (EACS). Guidelines. Version 8.0. October 2015. Available at: http://www.eacsociety.org/files/guidelines_8_0-english_web.pdf (last accessed 20 May 2016). 
74.
Mind Exchange Working Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the Mind Exchange Program. Clin Infect Dis 2013;56:1004-17. 
75.
Mind Exchange Working Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the Mind Exchange Program. Clin Infect Dis 2013;56:1004-17. 
76.
Detering K, Silvester W, Corke C, et al. Teaching general practitioners and doctors-in-training to discuss advance care planning: Evaluation of a brief multimodality education programme. BMJ Support Palliat Care 2014;4:313-21. 
77.
Detering KM, Hancock AD, Reade MC, et al. The impact of advance care planning on end of life care in elderly patients: Randomised controlled trial. BMJ 2010;340:c1345. 
78.
Mosack KE, Wandrey RL. Discordance in HIV-positive patient and health care provider perspectives on death, dying, and end-of-life care. Am J Hospice Palliative Med 2015;32:161-7. 
79.
Wenger NS, Kanouse DE, Collins RL, et al. End-of-life discussions and preferences among persons with HIV. JAMA 2001;285:2880-7. 
80.
Ludwig A, Chittenden E. Palliative care of patients with HIV. HIV InSite [Internet]. University of California San Francisco. 2008. Available at: http://hivinsite.ucsf.edu/InSite?page=kb-03-03-05 (last accessed 20 May 2016). 
81.
Detering K, Sutton E, Fraser S, et al. Feasibility and acceptability of advance care planning in elderly Italian and Greek speaking patients as compared to English-speaking patients: an Australian cross-sectional study. BMJ Open 2015;5:e008800.