Transcript Document

The patient with HIV/AIDS
in intensive care
Brendan McCarron
Millions
Estimated number of people living with
HIV globally, 1990–2007
40
30
Number
of people
20
living
with HIV
10
0
199019911992199319941995199619971998199920002001200220032004200520062007
Year
This bar indicates the range
1
Estimated number of adults and children
newly infected with HIV, 2007
Western &
Central Europe
Eastern Europe
& Central Asia
[19 000 – 86 000]
[70 000 – 290 000]
31 000
North America
46 000
150 000
East Asia
92 000
[38 000 – 68 000]
Middle East & North Africa
Caribbean
17 000
35 000
[16 000 – 65 000]
Sub-Saharan Africa
100 000
[47 000 – 220 000]
South & South-East Asia
340 000
[15 000 – 23 000]
Latin America
[21 000 – 220 000]
1.7 million
[1.4 – 2.4 million]
[180 000 – 740 000]
Oceania
14 000
[11 000 – 26 000]
Total: 2.5 (1.8 – 4.1) million
Estimated number of adults (15-59 years) living with HIV
(both diagnosed and undiagnosed) in the UK: 2008
Estimated number of people living HIV
25,000
24,350
Diagnosed
Undiagnosed
Total = 77,550 (73,000 - 83,300)
Excludes 5,450 HIV infections among
individuals outside the 15-59 years age range
20,000
15,000
13,850
10,000
8,950
6,550
5,450
5,000
4,050
2,850
4,550
2,250
2,150
1,200
450
550 150
0
MSM
Heterosexual
men born in
Africa
Heterosexual Heterosexual Heterosexual
women born in men born in women born in
Africa
UK/elsewhere UK/elsewhere
Injecting drug
user men
Injecting drug
user women
MESH Department - Centre for Infections
.
.
New HIV and AIDS diagnoses, people living with
diagnosed HIV, and deaths, among HIV-infected people,
UK: 1999-2008
70,000
Numbers with diagnosed HIV infection
HIV diagnoses
8,000
60,000
AIDS diagnoses
Deaths
7,000
50,000
6,000
5,000
40,000
4,000
30,000
3,000
20,000
2,000
10,000
1,000
0
0
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
MESH Department - Centre for Infections
People living with diagnosed HIV infection
New HIV and AIDS diagnoses and deaths
9,000
Number of new HIV diagnoses¹ by prevention group²,
UK: 1999-2008
4,500
4,000
New HIV diagnoses
3,500
MSM
Heterosexual contact in the UK
Heterosexual contact abroad
IDU
Blood product recipients
Mother-to-child transmission
3,000
2,500
2,000
1,500
1,000
500
0
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
¹ Numbers will rise as further reports are received, particularly for recent years
² Adjustments made for missing information relating to patient exposure
MESH Department - Centre for Infections
The HIV cycle
HIV/PNP/07/31367/1
CCR5 antagonists
Maraviroc
Reverse
transcriptase
rNA
NRTI
Fusion
inhibitors
T-20
enfuvirtide
dNA
protease
NNRTI
Nevirapine
Zidovudine
Efavirenz
Stavudine
Delavirdine
ddi
Etravirine
ddC
Abacavir
Integrase
Lamivudine
inhibitor
FTC-emtricatabine
Raltegravir
Tenofovir
CD4 cell
Saquinavir
Indinavir
Ritonavir Protease
Nelfinavir inhibitor
Lopinavir
Atazanavir
Tipranavir
Fosamprenavir
Amprenavir
Darunavir
Approval of Antiretrovirals: 1987-2006
ATV
FPV
ENF
FTC
25
20
15
NFV
RTV
DLV
IDV
NVP
10
EFV APV
ABC
TPV
DRV
LPV/ TDF
RTV
SQV
3TC
5
ZDV
0
1987
1987
ddI
ddC
d4T
Years
1991 1992 1993 1994 1995 1996
2006
2000
1988 1989 1990 1991
1996
1997 1998 1999 20
20002001
0
2002 2003 2004 2005 2006
Figure does not include fixed-dose combinations
Improving Outcomes With Evolving
Antiretroviral Regimens
CD4+
CD4+ RNA
RNA
Monotherapy
Monotherapy
Dual-NRTI
Dual-NRTIcombinations
combinations
HAART
HAART
300
200
100
0
0
–1
–2
–3
85
Acknowledgement: Cohen C. J.
Years
Change in HIV-1 RNA From Baseline
(log10 copies/mL)
Change in CD4+ Cell Count From Baseline
(cells/mm3)
400
Past




High pill burden
Food restrictions
Multiple daily doses
Poor tolerability
Present
HIV & Intensive Care

Drug delivery


Renal impairment


Some drugs available as suspensions, only AZT
is used i.v.
All NRTI (except ABC) need dose adjustment
Hepatic impairment


Some protease inhibitors need dose adjustment
Avoid nevirapine
Nucleoside Reverse
Transcriptase Inhibitors (NRTI)
Zidovudine Anaemia, myopathy, lipoatrophy
Stavudine Peripheral neuropathy, lipoatrophy
Didanosine Pancreatitis
Zalcitabine Peripheral neuropathy
Lamivudine/emtricabine
Abacavir
Hypersensitivity, CVD
Tenofovir Renal toxicity, nausea, osteoporosis/osteopenia
ALL CAUSE LACTIC ACIDOSIS
Mutations in mtDNA
Non-NRTI (NNRTI)
Delavirdine
Nevirapine
Efavirenz
Rash
Rash, abnormal LFTs
CNS excitation, insomnia
Protease inhibitor
Saquinavir
Ritonavir
Indinavir
Nelfinavir
Amprenavir
Atazanavir
Lopinavir
Darunavir
Nausea, vomiting, diarrhoea
Insulin resistance
Lipodystrophy
Hyperlipaemia
Diabetes
Increase in bilirubin
Drug interactions +++
D:A:D Study

23,000 prospective cohort study of HAART and
CHD


76,000 patient years median HAART exposure 4.5 years
MI incidence/1000 patient years








2.53 if <1 year of HAART
6.07 if >6 years of HAART
1.39 in Rx naïve patients
 HAART risk M=F; younger=older
Abacavir-90% increased risk of MI?
Rx at CD4 350
Renal disease
Bone disease
Neurocognitive deficit
Estimated late diagnosis of HIV infection by prevention
group among adults aged ≥ 15 years, UK: 2008
100%
CD4 cell counts <200 cells/mm³ within three months of diagnosis
90%
<200
Percentage diagnosed late
80%
<350
70%
65%
61%
60%
55%
52%
50%
43%
44%
40%
36%
30%
32%
30%
20%
20%
10%
0%
MSM
Number diagnosed = 2,760
Heterosexual men
1,630
Heterosexual women Injecting drug users
2,950
170
Overall
7,218
MESH Department - Centre for Infections
Late diagnosis of HIV infection
Patients with CD4 count under 200 cells/mm3 within 30 days of diagnosis.
Patients with a clinical AIDS diagnosis within 3 months of HIV diagnosis.
50%
47%
40%
37%
34%
Percent
diagnosed
late
28%
30%
22%
19%
20%
11%
10%
11%
10%
7%
0%
MSM
n=2356
Reports of HIV/AIDS diagnosis and CD4 Surveillance
IDUs
n=156
Female
heterosexuals
Male
heterosexuals
Overall
n=2571
n=1478
n=7450
Pattern of diagnosis and associated short-term
mortality rate among MSM
Number diagnosed
Short-term mortality rate
Diagnosed promptly
Diagnosed late
10%
2500
8%
2000
Short-term
mortality
6%
rate
(lines)
Number
diagnosed
(bars) 1500
Late diagnosis CD4 count <200 cells/mm3; prompt diagnosis ≥200 cells/mm3.
Short-term mortality rate: percent of patients known to have died within a year of diagnosis.
Reports of HIV diagnosis, deaths and CD4 cell counts
05
20
04
20
03
20
02
20
01
20
00
20
99
98
19
97
19
96
19
19
05
20
04
03
20
20
02
20
20
20
19
19
19
19
01
0%
00
0
99
2%
98
500
97
4%
96
1000
Who to test?
Opt-out Testing










GUM attendees
Antenatal clinics
TOP
History of IDU
Diagnosis of TB, HBV, HCV, Lymphoma
“Indicator Diseases”
Patients from high prevalence areas
MSM
Sexual partners of patients from high prevalence areas
Acute admissions & new patients registering at GP surgeries if
local undiagnosed prevalence > 1:1000
Indicator Diseases

AIDS Defining:


TB, PCP, Cerebral toxoplasmosis, PML, NHL,
Cervical cancer, CMV retinitis
Other conditions:

Bacterial pneumonia, lung cancer, AIN, VIN,
unexplained blood dyscrasias, oral candidiasis,
retinopathies, PUO,shingles, salmonellae
infections any STI
102 HIV-Patients admitted to UCLH ICU on
113 occasions
Diagnosis
N(%)
LRTI
54 (48)
PCP
 Bacterial pneumonia
 Tuberculosis
 Other

26
17
7
4
Neurological problems
16 (14)
Meningitis
 Cerebral Toxoplasmosis
 HIV Encephalitis
 Other
5
3
3
5

Sepsis
10 (9)
Post-cardiac arrest
7 (6)
Postoperative
7 (6)
Variceal haemorrhage
5 (4)
HAART-related
3 (3)
Miscellaneous
11 (10)
HIV and Intensive Care
Common ICU drugs contraindicated with
HAART
ICU Drug
HAART
Midazolam
Indinavir, Ritonavir, Tipranavir,
EFV
Amiodarone
Indinavir, Ritonavir, Tipranavir
Proton Pump Inhibitors
Atazanavir
H2-blockers
Atazanavir
Propanfenone
Lopinavir, Ritonavir, Tipranavir
Quinidine
Ritonavir, Tipranavir
Rifampicin
PIs, nevirapine
Enzyme Induction & Inhibition
HIV Drug Int
Needlestick Injuries


Report ASAP <1hour
The risks:






HBV 1:3
HCV 1:30
HIV 1:300
Serum for storage
Hepatitis B status
Risk assessed for PEP
Testing the Unconscious Patient


Always best practice is to obtain informed consent
Can consider testing the patient if it is in THEIR interests


“Unconscious patients
You may test unconscious patients for serious communicable diseases,
without their prior consent, where testing would be in their immediate clinical
interests - for example, to help in making a diagnosis. You should not test
unconscious patients for other purposes.”
- GMC “Serious Communicable Diseases” October, 1997
The issue of testing unconscious patients following a needlestick
injury is much more complex
 Human Tissue Act 2004
 Mental Capacity Act 2005
Confidentiality and Death

Who needs to know basis

Many don’t


Sexual contact-few others
Death certificates are in the public arena

Immunocompromise-more information available
later box useful
HIV Outcome





Now an eminently treatable condition
Near normal lifespan
If treated electively rather than after
presentation with an opportunistic infection,
2000
significantly less morbidity
Many complications now due to long term
exposure to drugs
Can improve care by offering more patients
testing with sentinel conditions
HIV Summary




HIV is becoming much more common, with
the greatest increase in the heterosexual
population.
Always offer patients with TB, HBV, HCV an
HIV test.
Consider offering patients a test when
presenting with sepsis or recurrent infections.
Consider testing in unexplained
lymphadenopathy, lymphopaenia and
hypergammaglobulinaemia.