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

Since the advent of combined antiretroviral therapy (cART) in
the mid-1990s, HIV-infected individuals have enjoyed progress-
ive 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 sus-
ceptible to drug-related adverse events.9 Moreover, older patients
Correspondence to: Dr Laura Waters, 1st Floor St Stephen’s
Centre – Chelsea & Westminster Hospital, 369 Fulham Road,
London SW10 9NH, UK
Email: lwaters@nhs.net
conditions10 increasing the risk of drug–drug 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 cardiovascu-
lar 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 inflammation, a well-established risk factor for
CVD, almost certainly plays a role. The role of immune senes-
cence, or accelerated immune ageing, is also unclear.
HIV-positive patients have more immune activation and more
immune senescence than HIV-negative controls, even on sup-
pressive ART, and both immune activation and senescence
are independently associated with surrogate markers of CVD.12
Although depression is not age-related, it is under-
diagnosed13 and older adults may be at greater risk of factors
associated with depression, such as social isolation.14
Additionally, depression is associated with cognitive abnormal-
ities 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 out-
patient 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
................................................................................................................................................

In the face of the issues outlined above, and an increasing Table 1 Routine assessments within the over 50 clinic
proportion of older patients in our HIV cohort, we have devel-
Test category Details
oped a dedicated outpatient clinic for HIV-infected individuals
aged 50 or older. We describe the development of this service, Blood tests Vitamin D (þ PTH if low), PSA (if not
checked by GP), testosterone (free
our current clinic protocols and a summary of selected service
and total), fasting glucose and lipids,
outcomes following the introduction of enhanced physical TDM as indicated
and psychological screening. Other clinical data 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
METHODS MDT if indicated), chest X-ray, faecal
occult bloods (if .60 and not
A multidisciplinary team consisting of a consultant, HIV nurse registered with GP) as per national
practitioner, specialist trainee doctor and pharmacist were guidelines,17 sexual health risk
tasked with setting up an ‘over 50 clinic’. Several meetings assessment and screening if
were held in conjunction with other members of the depart- indicated18
Cardiovascular assessment Estimated risk (JBS-2), coronary artery
ment as well as other specialties and from these a clinic tem-
(Figure 1) calcium score (CACS)
plate and protocol was developed; the clinic started in Bone assessments (Figure 2) Bone mineral density (BMD), bloods as
January 2009. The clinic consultant, specialist trainee and listed – see Figure 2
nurse practitioner each run a weekly clinic in conjunction, HIV-associated neurocognitive Generalized anxiety disorder
and a specialist pharmacist and dietician provide support. disorder (HAND) assessment questionnaire (GAD-7), depression
(Figure 3) questionnaire (PHQ-9), direct
Patients are referred in by their regular clinic doctor or nurse questioning to ascertain concerns
with age the only entry criterion. about memory/attention/cognition
At each appointment a thorough medical history, careful ( patient or others), revised every day
medication history and review of previous blood and urine memory questionnaire (EMQ-R),
International HIV Dementia Scale
results are performed. Additional assessments and investi-
(IHDS)
gations are listed in Table 1 with additional details described Medication assessments Adherence review (medication
in the following text: self-assessment, locally devised
questionnaire), careful
polypharmacy and drug –drug
interaction review
Blood tests Others Psycho social assessment, referral to
smoking cessation service as
A very high prostate specific antigen (PSA) is strongly sugges- appropriate. Female patients: review
tive of cancer; the significance of mild elevations is less clear. of cervical cytology and breast
PSA levels are interpreted according to age-related cut-offs screening
and referral to Urology services made if elevated.19 Data
PTH ¼ parathyroid hormone; PSA ¼ prostate specific antigen; GP ¼ general
suggest prostate cancer may be less common in HIV-infected practitioner; TDM ¼ therapeutic drug monitoring; PCR ¼ polymerase chain reaction;
men, although this may be secondary to reduced use of PSA EACS ¼ European AIDS clinical society; JBS ¼ Joint British Societies; ACR ¼
screening.20 Hypogonadism is common in HIV-infected men albumin:creatinine ratio; uACR ¼ urine ACR; uPCR ¼ urine protein:creatinine ratio
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 correlates well with estimated CV risk in HIV-infected sub-
method.22,23 Elevated fasting glucose (.6 mmol/L) prompts jects.26 CACS has limitations such as failing to detect non-
oral glucose tolerance testing and if impaired glucose tolerance calcified coronary plaques27 and may not be the optimal
or diabetes is confirmed, specialist referral made. Therapeutic marker of CV risk in HIV;28 however, after detailed discussion
drug monitoring (TDM) of selected ARVs (tenofovir, non- with the cardiology team at our centre, CACS was deemed the
nucleoside reverse transcriptase inhibitors, protease inhibitor most suitable method in the first instance. Patients undergo CT
[PI], maraviroc and raltegravir) is performed if indicated by
potential drug –drug interaction or toxicity.

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 pre-
ferred in our clinic as it includes more additional risk
factors.23 Framingham estimation may underestimate CV risk
in HIV-infected populations and HIV-specific 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 inflammatory markers,
measure of blood vessel reactivity and coronary artery Figure 1 Coronary artery calcium score (CACS) flowchart.
calcium score (CACS). CACS is predictive of future CV events TC ¼ total cholesterol in mmol/L; LDL ¼ low-density
lipoprotein-cholesterol in mmol/L
in large, prospective studies in the general population25 and

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548 International Journal of STD & AIDS Volume 23 August 2012
................................................................................................................................................
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 age-
and gender-matched cohort; further management or referral
depends on centile score as outlined in Figure 1. Only asympto-
matic 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 first 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 briefly ques-
tioned 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
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been shown to be reliable and accurate when compared with
formal anxiety assessments.30 GAD-7 shows excellent internal
consistency (Cronbach a ¼ 0.92), good test–re-test reliability
(intraclass correlation ¼ 0.83) and good correlation whether
self- and mental health professional (MHP)-administered (intra-
class correlation ¼ 0.83). GAD-7 also correlates well with two
other anxiety scales: the Beck Anxiety Inventory (r ¼ 0.72) and
the anxiety subscale of the Symptom Checklist-90 (r ¼ 0.74).
Finally, increasing GAD-7 scores correlate strongly with mul-
tiple 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 (Cronbach’s
a 0.86 –0.89) in different studies as is test–re-test reliability.
Self-completed PHQ-9 completed correlated well with repeat
questionnaire via telephone with an MHP (r ¼ 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 rec-
ommended.32 In our service a score greater than 5 prompts
 Waters et al. Clinics for HIV-positive individuals aged over 50 years 549
................................................................................................................................................

Figure 3 Assessment pathway for HIV-associated neurocognitive disorder. IHDS ¼ International HIV
Dementia Scale

repeat assessment in six months, a score of 10 or more referral Pharmacokinetics and drug interactions
to psychology and greater than 15 or more, referral to psychia-
Whether we should tailor antiretroviral dosing depending on
try services to consider pharmacotherapy.
age is unclear. However, it is well known that ageing is associ-
Patients are then questioned directly about their or
ated with changes in body functions and with a relative loss of
others’ concerns regarding memory, cognition or attention.
water and an increase in adipose tissue. The most important
Depending on the outcome of this discussion, symptomatic
pharmacokinetic change characterizing old age is a decrease
patients undergo further assessment with EMQ-R and
in the kidney excretory capacity. Tenofovir, which is renally
International HIV Dementia Scale (IHDS). With the EMQ-R,
excreted, has been shown to cause toxicity more frequently
patients rate 13 symptoms on a scale of 0 to 4 (0 ¼ once or
in older HIV-infected individuals.34 Alteration in the rate of
less in the last month; 4 ¼ once or more in a day); this is a
hepatic drug metabolism with advancing age is less clear and
simplified version of the original 28-point version and was
data on antiretroviral concentrations in older patients are
shown to be valid and reliable in a retrospective study;32 the
scarce. However, lopinavir, atazanavir and darunavir have all
original EMQ is very reliable (Cronbach’s a 0.91) and sensitive
been shown to achieve higher exposures in older individ-
to memory differences across different patient groups;
uals.35 – 37 The clinical consequences of these findings are
the revised version correlates very highly with the original
unclear and no recommendations, to date, exist on individual
(r ¼ 0.97). With EMQ-R, each question is divided into retrieval
dose adjustment in the ageing population. Nevertheless, the
(R) and attentional (A) items and cut-offs are provided for the
increased drug exposure in the elderly raises interest in the
total, R and A mean scores. The IHDS questionnaire screens
measurement of ARV drug plasma concentrations to monitor
for HIV-related dementia; as diagnosis depends on formal neu-
pharmacotherapy in this age group.
ropsychometric testing, screening questionnaires have been
Furthermore, TDM is useful in a population where polyphar-
developed to identify patients who require time-consuming
macy and the increased risk of significant drug interaction
formal assessment. Both the HDS and the IHDS were devel-
are common.38 Because of polypharmacy, collaboration with
oped to evaluate subcortical brain function as opposed to the
patients’ regular doctors is vital and one of the main
mini mental state examination, which predominantly assesses
objectives of the dedicated clinic is to strengthen communi-
cortical function. The IHDS was developed from the HDS as
cations with general practitioners (GPs) and social services
a cross-cultural tool to screen for HIV-associated neurocognitive
when needed.
disorder; a cut-off of 10 yields a sensitivity of 80% for diagnos-
ing dementia, compared with psychometric testing, in
resource-rich and poor settings.33 RESULTS
Patients with abnormal scores on EMQ-R and IHDS are
referred to psychology services for neuropsychometric testing;
General
those with abnormalities on one test only are reassured but if From the time of clinic inception (January 2009) to August 2011
still concerned may be offered further assessment. we have seen 150 patients. Seven percent were women

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550 International Journal of STD & AIDS Volume 23
................................................................................................................................................
and median (range) age was 58 (50–88) years. The commonest
ethnicity was white Caucasian (89%) followed by black African
(9%) and Asian (2%). Median (range) duration of HIV infection
was 14 (2–26) 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.
Coronary artery calcium score
Seventy individuals with no prior history of ischaemic heart
disease underwent assessment by CACS.
CAC scores revealed significant correlation with age
(P ¼ ,0.001) and Framingham risk scores (P ¼ 0.047). In our
care pathway, those with a CAC score greater than 75th percen-
tile 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.
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 con-
cerns had been noticed (by themselves or others). It was felt
screening asymptomatic individuals could lead to undue dis-
tress. 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 ques-
tionnaires. 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 admi-
nistered 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 scan-
ning (all normal) and have been referred for formal neuropsy-
chometric 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 first 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 inter-
preted with caution due to low numbers of female patients.
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August 2012
Table 2 Bone mineral density results
Male (n 5 111) Female (n 5 8) Overall (n 5 120)
Osteoporosis 17 (15%) 4 (50%) 21 (18%)
Osteopaenia 41 (37%) 3 (38%) 45 (38%)
Normal 53 (48%) 1 (12%) 54 (45%)
PSA results
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:
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 significant drug –drug interactions are as follows:
† Simultaneous intake of omeprazole 40 mg daily and ataza-
navir/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 concomi-
tant amlodipine 10 mg once daily or other calcium channel
blockers, resulting in CV adverse effects.
Therapeutic drug monitoring
TDM results for tenofovir (n ¼ 52), efavirenz (n ¼ 77) and dar-
unavir (n ¼ 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 ritonavir-
boosted darunavir was lower and drug exposure was higher
for patient’s older than 50 years of age, following once
daily dosing,40 confirming that it is essential to continue collect-
ing data for all currently used antiretrovirals over a wide age
range.
Tenofovir plasma concentrations correlated inversely with
estimated glomerular filtration rate, consistent with data
in the literature.41 Furthermore, increasing age was significantly
associated with lower tenofovir clearance and higher
plasma drug exposure.42 Patients older than 60 years showed
higher drug concentrations than younger individuals,
 Waters et al. Clinics for HIV-positive individuals aged over 50 years
................................................................................................................................................
suggesting the need for close renal function monitoring in this
population.
In terms if drug –drug interactions, to date 21% of individ-
uals attending the clinic have undergone an intervention
(dose adjustment or medication change to either their antiretro-
viral 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 attend-
ing 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 inflammation 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 oppor-
tunity of attending a dedicated over 50 clinic. This clinic
enables the ongoing assessment of targeted screening tests in
HIV-infected patients to best define 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 infor-
mation 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 assess-
ments 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 Stephen’s Centre, Chelsea and
Westminster Hospital for infrastructural and project support.
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551
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