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Journal of STD & AIDS

A dedicated clinic for HIV-positive individuals over 50 years of age: a multidisciplinary experience
L Waters, B Patterson, A Scourfield, A Hughes, S de Silva, B Gazzard, S Barton, D Asboe, A Pozniak and M Boffito
Int J STD AIDS 2012 23: 546
DOI: 10.1258/ijsa.2012.011412
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ORIGINAL RESEARCH ARTICLE

A dedicated clinic for HIV-positive individuals over 50 years

of age: a multidisciplinary experience
L Waters MRCP, B Patterson BNurs RGN, A Scourfield MRCP, A Hughes MRCP, S de Silva MRCP,
B Gazzard MD FRCP, S Barton FRCOG FRCP, D Asboe FRCP, A Pozniak MD FRCP and M Boffito MD PhD
Department of GU/HIV Medicine, Chelsea & Westminster Hospital, London, UK

Summary: The HIV-infected population is ageing. Issues including polypharmacy and co-morbidities led us to develop a dedicated
clinic for HIV-infected individuals over 50. We describe our service evaluation after two years. The over 50 clinic commenced in
January 2009. The team comprises a registrar, consultant, nurse practitioner and is supported by a pharmacist and mental health
services. Patients undergo a full medication and drug interactions review, neurocognitive assessment, adherence self-assessment
and investigations including therapeutic drug monitoring (TDM), coronary artery calcium scores (CACS) and bone mineral density.
Over two years of activity, 150 patients attended the service. Median (range) age was 58 (50 88), all were on combined antiretroviral
therapy and 38% (57/150) were on 3 non-HIV drugs. CACS was high (.90th centile) in 14%. Thirty-eight percent had osteopaenia
and 18% had osteoporosis requiring treatment. Thirteen out of 125 men had an increased prostate specific antigen, four were
diagnosed with prostate cancer. Drug interaction, TDM and neurocognitive assessments were useful for several patients.
Asymptomatic patients over 50 in long-term follow-up had new pathologies detected through targeted screening. The clinic has
improved general practitioner (GP) liaison and facilitated closer working relationships with other specialties. Patients have reacted
positively to the clinic, particularly as many do not routinely access their GP.
Keywords: HIV infection, ageing with HIV, multidisciplinary HIV clinic

INTRODUCTION
Since the advent of combined antiretroviral therapy (cART) in
the mid-1990s, HIV-infected individuals have enjoyed progressive reductions in HIV-associated morbidity and mortality.
Recent studies show marked improvements in life-expectancy
for patients with HIV1 and patients experiencing sustained
immune re-constitution on cART have a risk of mortality
similar to that of the general population.2 There has been a
shift from HIV-related to non-HIV-related morbidities3 and
HIV treating clinicians are dealing increasingly with an
ageing population. This is partly due to marked improvements
in life-expectancy4 but, in addition, patients are becoming
infected with HIV at an older age.5 Indeed, the Centers for
Disease Control and Prevention (CDC) have predicted that by
2015, 50% of HIV-infected individuals in the USA will be
older than 50 years of age.6
Older age is not a barrier to successful cART; in general, older
patients demonstrate better adherence,7 better virological
response rates but lower CD4 responses on cART.8 However,
age-related changes in drug absorption, distribution, metabolism
and excretion may render older HIV-infected patients more susceptible to drug-related adverse events.9 Moreover, older patients
Correspondence to: Dr Laura Waters, 1st Floor St Stephens
Centre Chelsea & Westminster Hospital, 369 Fulham Road,
London SW10 9NH, UK
Email: lwaters@nhs.net

are more likely to be receiving multiple drugs for co-morbid

conditions10 increasing the risk of drugdrug interactions,
particularly when more than one prescriber is involved.11
HIV-infected individuals are at greater risk of the morbidities
classically associated with increased age including cardiovascular disease (CVD), reduced bone mineral density (BMD) and
neurocognitive impairment (NCI). The precise mechanisms
for this increased risk are uncertain and likely multifactorial,
but chronic inammation, a well-established risk factor for
CVD, almost certainly plays a role. The role of immune senescence, or accelerated immune ageing, is also unclear.
HIV-positive patients have more immune activation and more
immune senescence than HIV-negative controls, even on suppressive ART, and both immune activation and senescence
are independently associated with surrogate markers of CVD.12
Although depression is not age-related, it is underdiagnosed13 and older adults may be at greater risk of factors
associated with depression, such as social isolation.14
Additionally, depression is associated with cognitive abnormalities and older HIV-infected patients with NCI are more likely
to have past or current depression than those without.15
Since 2003 our department has run a weekly Virtual Clinic;
this was set up to review patients failing therapy and treatment
complications. Over recent years the caseload has shifted from
reviewing virological failures and resistance, more to managing
antiretroviral (ARV) complications and co-morbidities; the outpatient team meetings, held prior to each clinical session, also
focused increasingly on the same challenges.

International Journal of STD & AIDS 2012; 23: 546 552. DOI: 10.1258/ijsa.2012.011412
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Waters et al. Clinics for HIV-positive individuals aged over 50 years

547

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In the face of the issues outlined above, and an increasing

proportion of older patients in our HIV cohort, we have developed a dedicated outpatient clinic for HIV-infected individuals
aged 50 or older. We describe the development of this service,
our current clinic protocols and a summary of selected service
outcomes following the introduction of enhanced physical
and psychological screening.

Table 1

Routine assessments within the over 50 clinic

Test category

Details

Blood tests

Vitamin D ( PTH if low), PSA (if not

checked by GP), testosterone (free
and total), fasting glucose and lipids,
TDM as indicated
Urine (uPCR and uACR) as per EACS
guidelines,16 height, weight, body
mass index and hip:waist ratio (with
referral to the dietician within the
MDT if indicated), chest X-ray, faecal
occult bloods (if .60 and not
registered with GP) as per national
guidelines,17 sexual health risk
assessment and screening if
indicated18
Estimated risk (JBS-2), coronary artery
calcium score (CACS)
Bone mineral density (BMD), bloods as
listed see Figure 2
Generalized anxiety disorder
questionnaire (GAD-7), depression
questionnaire (PHQ-9), direct
questioning to ascertain concerns
about memory/attention/cognition
( patient or others), revised every day
memory questionnaire (EMQ-R),
International HIV Dementia Scale
(IHDS)
Adherence review (medication
self-assessment, locally devised
questionnaire), careful
polypharmacy and drug drug
interaction review
Psycho social assessment, referral to
smoking cessation service as
appropriate. Female patients: review
of cervical cytology and breast
screening

Other clinical data

METHODS
A multidisciplinary team consisting of a consultant, HIV nurse
practitioner, specialist trainee doctor and pharmacist were
tasked with setting up an over 50 clinic. Several meetings
were held in conjunction with other members of the department as well as other specialties and from these a clinic template and protocol was developed; the clinic started in
January 2009. The clinic consultant, specialist trainee and
nurse practitioner each run a weekly clinic in conjunction,
and a specialist pharmacist and dietician provide support.
Patients are referred in by their regular clinic doctor or nurse
with age the only entry criterion.
At each appointment a thorough medical history, careful
medication history and review of previous blood and urine
results are performed. Additional assessments and investigations are listed in Table 1 with additional details described
in the following text:

Blood tests

Cardiovascular assessment
(Figure 1)
Bone assessments (Figure 2)
HIV-associated neurocognitive
disorder (HAND) assessment
(Figure 3)

Medication assessments

Others

A very high prostate specic antigen (PSA) is strongly suggestive of cancer; the signicance of mild elevations is less clear.
PSA levels are interpreted according to age-related cut-offs
and referral to Urology services made if elevated.19 Data
suggest prostate cancer may be less common in HIV-infected
men, although this may be secondary to reduced use of PSA
screening.20 Hypogonadism is common in HIV-infected men
and our local clinic policy recommends testing total and free
testosterone levels in all male patients.21 Fasting lipids are
used to estimate CV risk by the Joint British Societies (JBS)-2
method.22,23 Elevated fasting glucose (.6 mmol/L) prompts
oral glucose tolerance testing and if impaired glucose tolerance
or diabetes is conrmed, specialist referral made. Therapeutic
drug monitoring (TDM) of selected ARVs (tenofovir, nonnucleoside reverse transcriptase inhibitors, protease inhibitor
[PI], maraviroc and raltegravir) is performed if indicated by
potential drug drug interaction or toxicity.

PTH parathyroid hormone; PSA prostate specific antigen; GP general

practitioner; TDM therapeutic drug monitoring; PCR polymerase chain reaction;
EACS European AIDS clinical society; JBS Joint British Societies; ACR
albumin:creatinine ratio; uACR urine ACR; uPCR urine protein:creatinine ratio

correlates well with estimated CV risk in HIV-infected subjects.26 CACS has limitations such as failing to detect noncalcied coronary plaques27 and may not be the optimal
marker of CV risk in HIV;28 however, after detailed discussion
with the cardiology team at our centre, CACS was deemed the
most suitable method in the rst instance. Patients undergo CT

CV assessments
Several tools are available to estimate CV risk. Framingham
over-estimates CV risk in the general UK population;
Framingham-based assessments include JBS-2 which is preferred in our clinic as it includes more additional risk
factors.23 Framingham estimation may underestimate CV risk
in HIV-infected populations and HIV-specic models may
perform better.24 Because of this we elected to perform
additional CV risk assessment in our clinic. Surrogate
markers of CVD risk including serum inammatory markers,
measure of blood vessel reactivity and coronary artery
calcium score (CACS). CACS is predictive of future CV events
in large, prospective studies in the general population25 and

Figure 1 Coronary artery calcium score

TC total
cholesterol
in
mmol/L;
lipoprotein-cholesterol in mmol/L

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(CACS) flowchart.
LDL low-density

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Figure 2 Bone mineral density flowchart

scanning of the coronary vasculature and CACS is reported as

a centile by comparing the absolute score with an ageand gender-matched cohort; further management or referral
depends on centile score as outlined in Figure 1. Only asymptomatic patients are referred for CACS; any patient with
symptoms or signs suggestive of coronary artery disease are
investigated and referred in the usual manner.

Bone assessment
Low BMD is common in HIV-infected individuals29 and,
following meetings with the rheumatology team and careful
literature review, a local algorithm was devised (Figure 2).
This remains under regular review and will be adapted as
new evidence and guidance emerges.

Psychological and HIV-associated neurocognitive

disorder assessments
In the absence of clear consensus guidelines on how best to
investigate and manage NCI in HIV-infected individuals
we developed a protocol (Figure 3) in collaboration with our
psychology and psychiatry colleagues over a series of meetings.
The rst step is assessment of anxiety and depression (both can
be associated with NCI and may require correction before
further assessment is undertaken). All patients are briey questioned regarding any concerns (their own or others) about
memory, attention and cognitive function.
GAD-7 is a short, patient-completed questionnaire developed
as a screening tool for generalized anxiety disorder and has

been shown to be reliable and accurate when compared with

formal anxiety assessments.30 GAD-7 shows excellent internal
consistency (Cronbach a 0.92), good testre-test reliability
(intraclass correlation 0.83) and good correlation whether
self- and mental health professional (MHP)-administered (intraclass correlation 0.83). GAD-7 also correlates well with two
other anxiety scales: the Beck Anxiety Inventory (r 0.72) and
the anxiety subscale of the Symptom Checklist-90 (r 0.74).
Finally, increasing GAD-7 scores correlate strongly with multiple domains of functional impairment.30 The questionnaire
also performs moderately well with regard to other common
anxiety disorders: panic disorder, social anxiety disorder and
post-traumatic stress disorder. Patients are asked to grade
7 anxiety-related symptoms from 0 to 3; a score .10 prompts
referral to psychology.
PHQ-9 (patient health questionnaire) is also self-administered
and scores each of the nine Diagnostic and Statistical Manual
of Mental Disorders (DSM-IV) criteria for depression in a
similar way to GAD-7, from 0 (not at all) to 3 (nearly every
day). The internal reliability of PHQ-9 is excellent (Cronbachs
a 0.86 0.89) in different studies as is testre-test reliability.
Self-completed PHQ-9 completed correlated well with repeat
questionnaire via telephone with an MHP (r 0.84, mean
scores 5.08 versus 5.03). PHQ-9 score correlates well with
depression severity as assessed by MHP interview: 93% of
patients with no depressive disorder had a PHQ-9 score ,10
and 88% with major depression had scores of 10. There
is a strong association between increasing PHQ-9 score and
worsening functional ability.31
Depending on the score different courses of action are recommended.32 In our service a score greater than 5 prompts

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Waters et al. Clinics for HIV-positive individuals aged over 50 years

549

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Figure 3 Assessment pathway for HIV-associated neurocognitive disorder. IHDS International HIV
Dementia Scale

repeat assessment in six months, a score of 10 or more referral

to psychology and greater than 15 or more, referral to psychiatry services to consider pharmacotherapy.
Patients are then questioned directly about their or
others concerns regarding memory, cognition or attention.
Depending on the outcome of this discussion, symptomatic
patients undergo further assessment with EMQ-R and
International HIV Dementia Scale (IHDS). With the EMQ-R,
patients rate 13 symptoms on a scale of 0 to 4 (0 once or
less in the last month; 4 once or more in a day); this is a
simplied version of the original 28-point version and was
shown to be valid and reliable in a retrospective study;32 the
original EMQ is very reliable (Cronbachs a 0.91) and sensitive
to memory differences across different patient groups;
the revised version correlates very highly with the original
(r 0.97). With EMQ-R, each question is divided into retrieval
(R) and attentional (A) items and cut-offs are provided for the
total, R and A mean scores. The IHDS questionnaire screens
for HIV-related dementia; as diagnosis depends on formal neuropsychometric testing, screening questionnaires have been
developed to identify patients who require time-consuming
formal assessment. Both the HDS and the IHDS were developed to evaluate subcortical brain function as opposed to the
mini mental state examination, which predominantly assesses
cortical function. The IHDS was developed from the HDS as
a cross-cultural tool to screen for HIV-associated neurocognitive
disorder; a cut-off of 10 yields a sensitivity of 80% for diagnosing dementia, compared with psychometric testing, in
resource-rich and poor settings.33
Patients with abnormal scores on EMQ-R and IHDS are
referred to psychology services for neuropsychometric testing;
those with abnormalities on one test only are reassured but if
still concerned may be offered further assessment.

Pharmacokinetics and drug interactions

Whether we should tailor antiretroviral dosing depending on
age is unclear. However, it is well known that ageing is associated with changes in body functions and with a relative loss of
water and an increase in adipose tissue. The most important
pharmacokinetic change characterizing old age is a decrease
in the kidney excretory capacity. Tenofovir, which is renally
excreted, has been shown to cause toxicity more frequently
in older HIV-infected individuals.34 Alteration in the rate of
hepatic drug metabolism with advancing age is less clear and
data on antiretroviral concentrations in older patients are
scarce. However, lopinavir, atazanavir and darunavir have all
been shown to achieve higher exposures in older individuals.35 37 The clinical consequences of these ndings are
unclear and no recommendations, to date, exist on individual
dose adjustment in the ageing population. Nevertheless, the
increased drug exposure in the elderly raises interest in the
measurement of ARV drug plasma concentrations to monitor
pharmacotherapy in this age group.
Furthermore, TDM is useful in a population where polypharmacy and the increased risk of signicant drug interaction
are common.38 Because of polypharmacy, collaboration with
patients regular doctors is vital and one of the main
objectives of the dedicated clinic is to strengthen communications with general practitioners (GPs) and social services
when needed.

RESULTS
General
From the time of clinic inception (January 2009) to August 2011
we have seen 150 patients. Seven percent were women

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and median (range) age was 58 (5088) years. The commonest

ethnicity was white Caucasian (89%) followed by black African
(9%) and Asian (2%). Median (range) duration of HIV infection
was 14 (226) years, suggesting that the population included
both individuals with long-term infection and others
with more recent HIV acquisition. All patients seen were on
cART and 38% (57/150) were on three or more non-HIV
medications.

Table 2

Bone mineral density results

Osteoporosis
Osteopaenia
Normal

Male (n 5 111)

Female (n 5 8)

Overall (n 5 120)

17 (15%)
41 (37%)
53 (48%)

4 (50%)
3 (38%)
1 (12%)

21 (18%)
45 (38%)
54 (45%)

PSA results

Coronary artery calcium score

Seventy individuals with no prior history of ischaemic heart
disease underwent assessment by CACS.
CAC scores revealed signicant correlation with age
(P ,0.001) and Framingham risk scores (P 0.047). In our
care pathway, those with a CAC score greater than 75th percentile on age and sex matching qualify for lipid lowering therapy.
Fifteen (21%) individuals met these criteria, of these eight (53%)
had 10 year Framingham risk scores less than 20% so may have
been deemed otherwise of too low CV risk and eight (53%)
were not on lipid-lowering agents.

Of 127 men seen in the clinic since the introduction

of routine PSA measurement, 125 have results available.
Using age-adjusted cut-offs (age 50 59, PSA 3 ng/mL or
more; age 60 69, PSA 4 ng/mL or more; age 70 plus, PSA
more than 5 ng/mL),39 13 men had PSA values greater than
the upper limit of normal for their age. Outcomes are as
follows:

Four continue to be monitored in the over 50 clinic;

Four diagnosed with prostate adenocarcinoma, who were
referred for specialist management;
One repeated after three months and PSA normal;
Four treated with 30 days antibiotics:

Neuropsychometric assessment
The current neuropsychometric algorithm was introduced in
September 2010; after careful discussion, considering the lack
of guidance on screening for, and lack of interventions
to treat, NCI, we elected to screen only patients for whom concerns had been noticed (by themselves or others). It was felt
screening asymptomatic individuals could lead to undue distress. If guidance changes or new evidence emerges this will
be revised. Forty-six HIV-infected individuals were evaluated
between September 2010 and August 2011. Of these, median
age was 58 (range 50 74) years, 93% were men and 98%
were on ART. All were administered GAD-7 and PHQ-9 questionnaires. Twenty-four percent exhibited moderate to severe
anxiety by GAD-7 and of the three with severe anxiety, one
had already commenced amitryptiline and was experiencing
improvement, one was referred to psychiatry (outcome
pending) and one declined psychiatric assessment but did
agree to formal neuropsychometric testing (result pending).
By PHQ-9, 32% had moderate to severe depressive symptoms
were referred to their GP or to psychology services.
Twenty-one individuals reported concerns (theirs or others)
regarding memory, attention and cognition so were also administered EMQ and IHDS. EMQ scores were impaired in four
(19%) and IHDS scores were low (10) in six (30%). To date,
six have undergone brain magnetic resonance imaging scanning (all normal) and have been referred for formal neuropsychometric testing (results pending); for the remainder repeat
testing is planned. Longer-term follow-up is not available at
present but will be reviewed at a future date.

Bone mineral density

To date, 120 individuals have undergone dual-energy X-ray
absorptiometry scanning for the rst time, 118 men and eight
women. The rates of osteoporosis and osteopaenia, overall
and by gender, are shown in Table 2. Low BMD appears very
common in women although these results should be interpreted with caution due to low numbers of female patients.

W One normalized;
W One awaiting outcome;
W Two PSA remained high and under urology follow-up.

Polypharmacy and drug drug interaction

assessment
Overall, 50% of the patients seen were on polypharmacy.
Examples of signicant drug drug interactions are as follows:

Simultaneous intake of omeprazole 40 mg daily and atazanavir/ritonavir 300/100 mg once daily;

Simvastatin 40 mg daily with and nevirapine 400 mg daily
and no cholesterol response;
Darunavir/ritonavir 800/100 mg once daily with concomitant amlodipine 10 mg once daily or other calcium channel
blockers, resulting in CV adverse effects.

Therapeutic drug monitoring

TDM results for tenofovir (n 52), efavirenz (n 77) and darunavir (n 34) were reviewed. In our small cohort of older
HIV-infected individuals, plasma concentrations of efavirenz
were not markedly different when compared with data in
younger patients.40.
On the other hand, the predicted clearance of ritonavirboosted darunavir was lower and drug exposure was higher
for patients older than 50 years of age, following once
daily dosing,40 conrming that it is essential to continue collecting data for all currently used antiretrovirals over a wide age
range.
Tenofovir plasma concentrations correlated inversely with
estimated glomerular ltration rate, consistent with data
in the literature.41 Furthermore, increasing age was signicantly
associated with lower tenofovir clearance and higher
plasma drug exposure.42 Patients older than 60 years showed
higher drug concentrations than younger individuals,

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Waters et al. Clinics for HIV-positive individuals aged over 50 years

551

................................................................................................................................................

suggesting the need for close renal function monitoring in this

population.
In terms if drug drug interactions, to date 21% of individuals attending the clinic have undergone an intervention
(dose adjustment or medication change to either their antiretroviral or the co-administered non-antiretroviral drug).

SERVICE DEVELOPMENT
Our over 50 clinic remains under regular review and screening
procedures are updated regularly. As well as optimizing
current, and introducing new, screening procedures, this
clinic provides an ideal opportunity to carry out age-related
research, audit and service evaluation. All individuals attending the clinic are offered the possibility of signing a written
consent form to allow publication of data emerging from the
Clinic. Planned service developments include the possibility
of introducing routine anal cytology and we are planning to
commence a research project investigating serological markers
of inammation among clinic attendees. Finally, as we plan
to continue and expand the service we will be consulting
with GPs and plan to involve primary care representatives on
an ongoing basis.

CONCLUSIONS
HIV-infected individuals aged 50 years or older in long-term
follow-up at Chelsea and Westminster Hospital have the opportunity of attending a dedicated over 50 clinic. This clinic
enables the ongoing assessment of targeted screening tests in
HIV-infected patients to best dene their clinical utility and
cost-effectiveness. Improved knowledge on HIV and ageing
through such methods will facilitate clearer screening
guidelines for HIV-infected patients and development of
future care pathways, particularly in community and GP
settings.
In our two-year experience, HIV-infected patients over 50
years of age were found to have pathologies only detected by
targeted screening. The clinic has served to improve GP
liaison and closer working relationships with other specialties.
Important limitations include lack of longer-term follow-up,
particularly with regard to CV and neurocognitive assessment;
these data will be reviewed regularly and we expect more information on outcomes with time. In addition, in the absence of a
formal comparative study we cannot state that outcomes have
improved within this service. However, most of the assessments are recommended in consensus guidelines and we
have highlighted cases where a serious condition may have
remained otherwise undetected.
The majority of patients reacted positively to the clinic,
particularly as many do not routinely access their GP.

ACKNOWLEDGEMENTS

The authors thank Stuart Yau, Amena Ahmed, Dr Muge

Cevik, from Chelsea and Westminster Hospital and Dr Laura
Dickinson and Prof David Back, from the University of
Liverpool for their help in collecting and interpreting
some of the clinic observations. Also thanks to the HIV/GUM
Department and St Stephens Centre, Chelsea and
Westminster Hospital for infrastructural and project support.

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(Accepted 12 April 2012)