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Revised presentation format

HIV+ adult patients= : West Africa vs London
autopsies 1989-1995 - pre-HAART

Pneumocystis pneumo= nia

CMV & toxoplasm= a CNS disease

Miliary MAC infecti= on

BHIVA Audit: 133 participating centres

Information on deat= hs

Information on deat= hs (cont)

Reviews of HIV deat= hs

Death review proces= s

BHIVA Audit Case no= te review

Patient demographic= s

Age and place of de= ath

CD4 and VL in last = six months of life

Immediate cause of = death

UK HIV & AIDS d= ata: 1985-2004

Scenario leading to= death

Deaths not directly related to HIV

Scenario leading to= death

conclusion<= /font>

Malignancy deaths w= ere as follows:

Cardiovascular dise= ase

Late diagnosis: ove= rall impact

Late-diagnosis: pat= ient characteristics

UK residency and NHS entitlement

Late diagnosis: cau= ses of death

Late diagnosis: cli= nician delay

Late diagnosis: HIV testing in the ill patient

Late diagnosis: HIV testing in the ill patient, cont

HIV drug resistance=

Starting HAART<= /b>

Catastrophic crypto= coccal IRIS

Adverse reactions to therapy

Catastrophic events=

Patient factors=

Patient factors: ca= uses of death due to poor adherence

Patient factors, co= nt.

Tonsil & rectal biopsy

Autopsy and review<= /a>

Basic coronial law.=
Coroners Act 1988: ss8, 19, 20

Certification of de= aths due to HIV

Death certification, cont.

Conclusions from the BHIVA audit

Conclusions, cont.<= /a>

Conclusions, cont.<= /a>

Conclusions, cont.<= /a>

Conclusions, cont.<= /a>

Recommendations=

Personal cases from= 2006

Personal cases from= 2006

Slide 51

Slide 52

Non-cirrhotic portal hypertension

CD8 encephalitis

MOF & Pulmonary leukostasis –
HHV8+ polyclonal LPD

DD of miliary lung lesions

Personal conclusion=

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Revised presentation format
BHIVA mortality aud= it - the year 2005
BHIVA Audit & S= tandards Sub-Committee
Hilary Curtis
25 years on: the ca= uses of death in HIV-related disease
Introduction of the= BHIVA standards document
Margaret Johnson

HIV+ adult patients= : West Africa vs London
autopsies 1989-1995 - pre-HAART

Pneumocystis pneumo= nia

CMV & toxoplasm= a CNS disease

Miliary MAC infecti= on

BHIVA Audit: 133 participating centres
80% outside the NHS= London region, 19% in the London region
58% serve >100 p= atients
19% 1-50 HIV patien= ts,
23% 51-100,<= /td>
20% 101-200,=
21% 201-500,=
17% more than 500 p= atients.
40 (30%) centres re= ported no deaths among their adult HIV patients in the preceding year, including 52= % of those serving 100 or fewer patients.

Information on deat= hs
Respondents were as= ked how they find out when HIV patients under their care die in the community:<= /td>
61% via grapevine/w= ord of mouth
49% via routine fol= low-up
41% via community H= IV team
13% formal network = meetings
21% other.

Information on deat= hs (cont)
When asked how they= would find out if HIV patients referred to tertiary/specialist services had died:
34% did not answer<= /font>
20% described activ= e follow up
26% described passi= ve receipt of feedback
3% gave answers sug= gesting they might not always know

Reviews of HIV deat= hs
Centre policies on = reviewing deaths among adult patients receiving HIV care:
24% formally review= all deaths
11% review in speci= fic circumstances
20% review if clini= cians have concerns
39% no clear policy=

Death review proces= s
22% of centres invo= lve hospital/community multi-disciplinary team
28% hospital multi-= disciplinary team
28% medical team on= ly
8% other
14% no answer.
At 48% of centres a= t least some reviews involve discussing the death at a meeting.  Other methods include reading case no= tes.

BHIVA Audit Case no= te review
89 centres submitte= d case note review data for 397 deaths among adults with HIV:
10 excluded<= /td>
 387 deaths were analysed.

Patient demographic= s

Age and place of de= ath

CD4 and VL in last = six months of life

Immediate cause of = death

UK HIV & AIDS d= ata: 1985-2004

Scenario leading to= death

Deaths not directly related to HIV
123 (32%) of deaths= were considered not directly HIV-related.  These comprised:
30 (7.8% of all dea= ths) malignancies
22 (5.7%) liver dis= ease
17 (4.4%) CVD
7 (1.8%) suicide
7 (1.8%) sepsis
6 (1.6%) accident/i= njury, including one homicide
4 (1.0%) overdose
1 (0.3%) renal dise= ase
29 (7.5%) other or = not stated.

Scenario leading to= death

conclusion<= /font>
2/3 to 3/4   HIV+ deaths are HIV-related
Medico-politically = important

Malignancy deaths w= ere as follows:
29 lymphoma*=
6 liver (of which 2= reported as liver disease rather than malignancy)
6 lung or bronchus<= /font>
3 anal*
2 adenocarcinoma
2 kidney
2 oesophagus=
2 penis
2 prostate
1 each bladder, bow= el, breast, cervix*, Merkel cell, multiple myeloma, pancreas
5 not known or not = stated**

Cardiovascular dise= ase
CVD was the immedia= te cause of death for 25 (6.5%) patients. This was not all IHD:
2 HIV-related pulmo= nary hypertension
1 sub-arachnoid hae= morrhage in alcoholic patient with cardiomyopathy
3 other cardiomyopa= thy
1 viral myocarditis= .
17 of the 25 CVD de= aths were classified by the reporting centre as not related to HIV.

Late diagnosis: ove= rall impact
 88 (23%) deaths were reported as due t= o HIV diagnosis too late for effective treatment
 5 further deaths occurring within 3 mo= nths of diagnosis were reclassified as due to late diagnosis, giving a total o= f 93 (24% of all deaths, 35% of HIV-related deaths)
This is a minimum a= s some deaths attributed to untreatable complications of HIV involved conditions which early treatment could have prevented.  Also, there may be under-ascertainment of deaths occurring without involvement of HIV specialist services.

Late-diagnosis: pat= ient characteristics
Among patients whos= e deaths were attributed to late diagnosis of HIV:
10.8% were aged und= er 30 compared with 5.8% dying in other scenarios
31.2% were white co= mpared with 65.0% dying in other scenarios.

UK residency and NHS entitlement
12 patients were kn= own to have arrived in the UK within six months of death:
9 died as a result = of late diagnosis of HIV
One death was not d= irectly related to HIV (hepatocellular carcinoma, hepatitis B/C co-infection).
No deaths were repo= rted as due to treatment being delayed or denied because of ineligibility for NHS car= e.

Late diagnosis: cau= ses of death
28 PCP
16 OI
9 TB
8 lymphoma
8 sepsis
7 multi-organ HIV
3 KS
3 CVD
2 renal
1 malignancy=
6 other or multiple= HIV related
2 not known<= /td>

Late diagnosis: cli= nician delay
In 16/93 cases, the= narrative suggested possible clinician delay in diagnosing HIV after the patient had presented with symptomatic illness:
8 (50%) of these pa= tients were over 50yrs at death (7 of whom were white), compared with 96 (26%) of other de= aths
?ageism

Late diagnosis: HIV testing in the ill patient
Two cases of clinic= ian delay in diagnosis raise questions about HIV test procedures for ill in-patients:<= /font>
Case 1:
Admitted with weigh= t loss and diarrhoea.  Diagnosed HIV+ by GUM health advisor while on general medical ward
Unclear why the med= ical team did not test for HIV without requiring involvement of GUM health advisor.=

Late diagnosis: HIV testing in the ill patient, cont
Case 2: Presented w= ith PUO 3/52 before GU involved.  Xray showed features of PCP months before admission.  Case was formally reviewed at Grand Round which concluded that “se= xual history taking should be mandatory” as part of PUO investigation.<= /td>
Unclear why sexual = history taking was identified as the priority, rather than HIV testing.

HIV drug resistance=
Eleven (3%) deaths = were attributed to running out of treatment options with MDR HIV.

Starting HAART<= /b>
Six deaths resulted= from new or worsening disease soon after starting HAART, including three due to crypt= ococcal meningitis.
These deaths may ha= ve included cases of IRIS.

Catastrophic crypto= coccal IRIS

Adverse reactions to therapy
Five deaths were re= ported as definite or probable adverse reactions to HIV-related therapy:
3 lactic acidosis
1 fulminant liver f= ailure attributed to isoniazid
1 pneumonia possibl= y associated with non-Hodgkins lymphoma chemotherapy-related bone marrow suppression.<= /font>

Catastrophic events=
Seven deaths were c= lassified as catastrophic events in patients on treatment:
3 lactic acidosis += 1fulminant liver failure (from previous adverse events slide)
1 MI - strong famil= y history not recognised because adopted
1 right temporal lo= be infarction secondary to VZV vasculitis
1 pulmonary embolus= .

Patient factors=
Patient choice not = to receive treatment accounted for 18 deaths.  At least 3 had previously taken ART.
26 deaths were dire= ctly attributed to treatment being ineffective through poor adherence.<= /td>
A history of poor a= dherence was noted in five other cases – 3 where death was attributed to running out of treatment options for MDR HIV and 2 attributed to untreatable complications.  Poor attendance w= as noted in 2 further untreatable complications cases.

Patient factors: ca= uses of death due to poor adherence
12 sepsis
2 PCP
2 multi-organ HIV
1 KS
1 systemic leishman= iasis
1 PML
1 dementia
1 pulmonary hyperte= nsion
1 disseminated MAI<= /font>
1 presumptive MTB
1 cerebral toxoplas= mosis + nosocomial bronchopneumonia
1 died with severe = muscle wasting / diarrhoea
1 “advanced HIV dis= ease”

Patient factors, co= nt.
13 patients with a = previous positive HIV test had not been under regular care and re-presented too la= te for effective treatment (including one who had not returned to receive the test result).
4 patients who were= diagnosed late with HIV were reported to have previously refused testing.

Tonsil & rectal biopsy

Autopsy and review<= /a>
Autopsy were known = to have been done in 57 (15%) cases.
Of these, 41 were c= oronial, 11 consented and information was missing for 5.
Refusal of consent = was cited as a reason for not performing a PM in 22 cases.
Lack of access to p= athology was cited in 13 cases from 7 centres.

Basic coronial law.=
Coroners Act 1988: ss8, 19, 20
Duty to hold an inq= uest if deceased
Has died a violent = or an unnatural death
Has died a sudden d= eath of which the cause is unknown
Has died in prison,= psychiatric hospital etc
Purpose of an autop= sy
To exclude the need= for inquest if COD is ‘natural’
To provide evidence= for the inquest if COD appears to be ‘unnatural’

Certification of de= aths due to HIV
According to the ce= ntre questionnaire:
 60% of respondents always write HIV on= the certificate and/or tick the box to indicate more information available
 1% sometimes neither write HIV nor tic= k the box
 35% have not certified HIV deaths
 5% were not sure or did not answer.

Death certification, cont.
However, in the cas= e note review, HIV was not written on the certificate and the box was not ticked= in 39 (10%) cases.
Only 12 of these 39= deaths were reported as not directly related to HIV (a further 4 were re-classified as such during the audit)
Information about t= he certificate was lacking in 195 (50%) cases.

Conclusions from the BHIVA audit
Late diagnosis and = causes not directly related to HIV account for the majority of deaths in adults with HIV.
There is some evide= nce of clinician delay in diagnosing HIV.
Deaths due to adver= se reactions to HIV therapy and to running out of options with MDR HIV are reassuringly rare.

Conclusions, cont.<= /a>
 Specific causes of death are predomina= ntly:
“Classical AIDS” in= cluding PCP, sepsis, lymphoma and TB
Malignancies=
Liver disease due t= o hepatitis B/C co-infection and/or alcohol
Cardiovascular dise= ase.

Conclusions, cont.<= /a>
This study has iden= tified some specific issues, including:
Mechanisms for info= rming centres when patients have died in the community or at tertiary referral centres
Importance of good communication and prompt, effective referral pathways
Value of death revi= ews
Awareness of lactic= acidosis
Need for improvemen= t in death certification.

Conclusions, cont.<= /a>
A limitation of thi= s study is that data was collected via HIV clinicians, who may not have known of all deaths. Under-ascertainment may be more likely for:
Deaths from late-di= agnosed or undiagnosed HIV disease in community or general medical settings.<= /td>
Deaths in the commu= nity of external causes such as suicide or drug overdose.

Conclusions, cont.<= /a>
For some centres, d= ata gathering for this study has been an instructive exercise in itself, and = has identified issues of communication and record-keeping.

Recommendations=
BHIVA requests its = members to discuss these findings at local grand rounds, to communicate the impact of late HIV diagnosis to non-HIV clinicians and jointly consider how to facilitate rapid diagnosis and transfer of patients to specialised HIV ca= re.
BHIVA asks EAGA and= the Department of Health to consider how to promote more routine HIV testing = in generic services as well as specialist HIV/GU/sexual health settings.

Personal cases from= 2006
Encephalitis ?cause=
Subtentorial PML
CD8 encephalitis
CNS toxoplasma &= ; MDRTB
Occult pulmonary KS=
Disseminated KS
Toe gangrene, MRSA = sepsis, TMA
Cellulitis, aortic = mycotic aneurysm
MOF ?cause
TMA, MOF
Pneumocystis – untr= eatable
Disseminated VZV, M= OF (2)
CNS & pulmonary= toxoplasma
Disseminated Ca cer= vix
Occult lymphoma, HP= S, MOF
LPD, TMA, MOF
Ischaemic heart dis= ease
IVDU, amyloid renal= failure
Non-cirrhotic porta= l H/T (2)
HBV cirrhosis

Personal cases from= 2006
Encephalitis ?cause=
Subtentorial PML
CD8 encephalitis
CNS toxoplasma &= ; MDRTB
Occult pulmonary KS=
Disseminated KS
Toe gangrene, MRSA = sepsis, TMA
Cellulitis, aortic = mycotic aneurysm
MOF ?cause
TMA, MOF
Pneumocystis – untr= eatable
Disseminated VZV, M= OF (2)
CNS & pulmonary= toxoplasma
Disseminated Ca cer= vix
Occult lymphoma, HP= S, MOF
LPD, TMA, MOF
Ischaemic heart dis= ease
IVDU, amyloid renal= failure
Non-cirrhotic porta= l H/T (2)
HBV cirrhosis

Slide 51

Slide 52

Non-cirrhotic portal hypertension

CD8 encephalitis

MOF & Pulmonary leukostasis –
HHV8+ polyclonal LPD

DD of miliary lung lesions
TB
Fungi
Bacteria
Nocardia
Herpes – HSV, VZV
Toxoplasma gondii
Carcinoma, lymphoma=
[IVDU particle nodu= les]

Personal conclusion=
Undoubted shifts in= patterns of HIV disease
Medicine – diagnost= ic + management - is difficult
MOF syndromes
Sepsis, including T= B
TMA
HHV8
HPS etc
Cause of death asce= rtainment is always imperfect

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