The patient with HIV/AIDS in intensive care

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The patient with HIV/AIDS in intensive care

• Brendan McCarron

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Estimated number of adults and children newly
infected with HIV, 2007
Total 2.5 (1.8 4.1) million
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The HIV cycle
HIV/PNP/07/31367/1
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CCR5 antagonists
Maraviroc
Reverse transcriptase
protease
rNA
dNA
NNRTI
NRTI
Nevirapine Efavirenz Delavirdine Etravirine
Saquinavir Indinavir Ritonavir Nelfinavir Lopinavi
r Atazanavir Tipranavir Fosamprenavir Amprenavir D
arunavir
Zidovudine Stavudine ddi ddC Abacavir Lamivudine F
TC-emtricatabine Tenofovir
Fusion inhibitors
Protease inhibitor
T-20 enfuvirtide
Integrase inhibitor
Raltegravir
CD4 cell
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Approval of Antiretrovirals 1987-2006
ATV FPV ENF FTC
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DRV
TPV
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LPV/RTV
TDF
APV
EFV ABC
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NFV DLV
RTV IDV NVP
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SQV 3TC
5
d4T
ddC
ddI
ZDV
0
Years
1996
1987
1991
2000
2006
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2020000
2001
2002
2003
2004
2005
2006
Figure does not include fixed-dose combinations
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Improving Outcomes With Evolving Antiretroviral
Regimens
400
CD4 RNA
CD4 RNA
Monotherapy
Monotherapy
Dual-NRTI combinations
Dual-NRTI combinations
300
HAART
HAART
200
100
Change in HIV-1 RNA From Baseline (log10
copies/mL)
Change in CD4 Cell Count From Baseline
(cells/mm3)
0
0
1
2
3
85
Years
Acknowledgement Cohen C. J.
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Past

• High pill burden
• Food restrictions
• Multiple daily doses
• Poor tolerability

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Present
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HIV Intensive Care

• Drug delivery
• Some drugs available as suspensions, only AZT is
  used i.v.
• Renal impairment
• All NRTI (except ABC) need dose adjustment
• Hepatic impairment
• Some protease inhibitors need dose adjustment
• Avoid nevirapine

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Nucleoside Reverse Transcriptase Inhibitors (NRTI)
Zidovudine Anaemia, myopathy, lipoatrophy Stavudin
e Peripheral neuropathy, lipoatrophy Didanosine Pa
ncreatitis Zalcitabine Peripheral
neuropathy Lamivudine/emtricabine
Abacavir Hypersensitivity, CVD Tenofovir
Renal toxicity, nausea, osteoporosis/osteopenia A
LL CAUSE LACTIC ACIDOSIS Mutations in mtDNA
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Non-NRTI (NNRTI)
Delavirdine Rash Nevirapine Rash, abnormal
LFTs Efavirenz CNS excitation, insomnia
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Protease inhibitor
Saquinavir Nausea, vomiting, diarrhoea Ritonavir
Insulin resistance Indinavir Lipodystrophy Nelfin
avir Hyperlipaemia Amprenavir Diabetes Atazanavi
r Increase in bilirubin Lopinavir Drug
interactions Darunavir
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DAD 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 lt1 year of HAART
• 6.07 if gt6 years of HAART
• 1.39 in Rx naïve patients
• HAART risk MF youngerolder
• Abacavir-90 increased risk of MI?
• Rx at CD4 350
• Renal disease
• Bone disease
• Neurocognitive deficit

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Late diagnosis of HIV infection
n2356 n156
n2571 n1478
n7450
Reports of HIV/AIDS diagnosis and CD4
Surveillance
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Pattern of diagnosis and associated short-term
mortality rate among MSM
Number diagnosed
Short-term mortality rate
Diagnosed promptly
Diagnosed late
Late diagnosis CD4 count lt200 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
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Who to test?
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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 gt 11000

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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

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102 HIV-Patients admitted to UCLH ICU on 113
occasions
Diagnosis N()
LRTI PCP Bacterial pneumonia Tuberculosis Other 54 (48) 26 17 7 4
Neurological problems Meningitis Cerebral Toxoplasmosis HIV Encephalitis Other 16 (14) 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)
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HIV and Intensive Care
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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
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Enzyme Induction Inhibition
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HIV Drug Int
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Needlestick Injuries

• Report ASAP lt1hour
• The risks
• HBV 13
• HCV 130
• HIV 1300
• Serum for storage
• Hepatitis B status
• Risk assessed for PEP

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Testing the Unconscious Patient

• Always best practice is to obtain informed
  consent
• Can consider testing the patient if it is in
  THEIR interests
• Unconscious patientsYou 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

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Confidentiality and Death

• Who needs to know basis
• Many dont
• Sexual contact-few others
• Death certificates are in the public arena
• Immunocompromise-more information available later
  box useful

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HIV Outcome

• Now an eminently treatable condition
• Near normal lifespan
• If treated electively rather than after
  presentation with an opportunistic infection,
  significantly less morbidity
• Many complications now due to long term exposure
  to drugs
• Can improve care by offering more patients
  testing with sentinel conditions

2000
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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.