Transcript immunocompromise

HIV
The Human immunodeficiency virus
Retrovirus
RNA virus
Protein coat (HIV antigens)
Reverse transcriptase turn RNA into
DNA
HIV integrase incorporates viral DNA into
host genome
Transcribed by host/viral enzymes
Viral assembly and shedding with
protease
Pathophysiology
Transmission :
- sexual
- nonsexual
Categorization of HIV exposures
Group 1 HIV antibody positive –
asymptomatic
 Group 2 ARC, CD4 < 400
symptoms (fever, malaise,
lymphadenopathy, diarrhea),
opportunistic infections
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Categorization of HIV
exposures
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Group 3
AIDS; CD4 < 200
Kaposi’s sarcoma,
lymphoma,
pneumonia,
cervical carcinoma,
etc.
Signs and symptoms
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Initial exposure or infection
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Flulike symptoms-fever, weakness, 10 to 14
days
Asymptomatic stage
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serologic evidence of infection
no signs or symptoms
Signs and symptoms
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Symptomatic stage
serologic evidence of infection
 T4/T8 ratio reduced to about 1
 persistent lymphadenopathy
 oral candidiasis
 constitutional symptoms :
night sweats, diarrhea, weight loss, fever
malaise, weakness
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Signs and symptoms
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Advanced symptomatic stage
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serologic evidence of infection
T4/T8 ratio < 0.5
HIV encephalopathy
HIV wasting syndrome
major opportunistic infections
Neoplasms : kaposi’s sarcoma, lymphoma
Laboratory
blood, semen, breast milk, tears, saliva
 With or without clinical : antibodies
 Advanced HIV :
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altered ratio T4/T8
decreased total number of lymphocytes
trombocytopenia, anemia
alteration in Ab system
Cutaneous anergy
Laboratory test
ELISA : sensitive, high rate of false
positive
screen
 Second test : Western blot
 Combination of test : > 99% accurate
 Positive : exposed to AIDS virus
potentially infectious
 PCR
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Laboratory test
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Status and potential risk of surgery
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Viral load
CD4 lymphocyte count
Laboratory test
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Viral load
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Current viral activity
Disease progression
> 30,000 – 50,000 HIV RNA copies/ml
plasma
poor prognosis
 < 5000 HIV RNA copies/ml plasma
better short-term prognosis
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Laboratory test
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CD4 lymphocyte
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Degree of immunologic destruction
AIDS :
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low lymphocyte count and
depressed CD4 T-cells
CD4 : CD8 ratio of 1:0 or less
Opportunistic infection
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Pneumocystis carinii pneumonia (PCP)
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Protozoan parasite
Invade lungs (rarely LN)
Symptoms : fever, cough, difficulty
breathing, weight loss, night sweats,
fatigue
Prophylaxis : TMP-SMX,
Opportunistic infection
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Toxoplasmosis
Protozoa
 Infection of CNS
 Symptoms : neurologic
headaches, dizziness, seizures
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Opportunistic infection
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Cryptosporidiosis
Protozoa
 Affect GI tract
Nausea, vomiting, diarrhea, malaise, fever,
weight loss
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Opportunistic infection
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Candidiasis
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Oral and systemic
Infect mucous membrane : mouth, vagina,
esophagus, GI tract, skin
Systemic Tx. Fluconazole or
ketoconazole
Opportunistic infection
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Cryptococcus and histoplasma
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Yeastlike fungi
Infect lung and brain, other tissue
Fever, weight loss, neurologic symptoms,
difficulty breathing, mucosal lesion,
headache, N/V, malaise
Tx. : fluconazole, ketoconazole,
amphotericin B
Opportunistic infection
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Tuberculosis
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Mycobacterium tubercullosis
S/S : lymphadenopathy, cough, fever
weight loss, diarrhea, night sweats,
malaise
Skin test
Tx : Isoniazid (INH), Rifampin,
ethambutol, streptomycin
Opportunistic infection
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Tuberculosis
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Multiantibioticresistant form of TB
Mycobacterium avium
Mycobacterium intracellulare
Tx. : ciprofloxacin, amikacin sulfate,
ethambutol
Opportunistic infection
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Cytomegalovirus
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90% of HIV
Oral cavity : deep, non-healing ulcerations
Retinitis
Esophagitis
Colitis
Tx. : Ganciclovir
Opportunistic infection
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Herpes simplex/ herpes zoster
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Infect epithelial tissue and nerve ending
Symptoms: painful inflammatory blisters
follow a sensory nerve tract
Tx./prophylaxis : acyclovir
Opportunistic infection
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Epstein-Barr virus
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Associated with oral hairy leukoplakia in
HIV/AIDS
Acyclovir or ganciclovir
Opportunistic infection
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Human papillomavirus
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Oral cavity
Clinical : oral warts
Tx. excision
HAART therapy
Highly Active Anti-Retroviral Therapy
 Is essentially triple (or even quadruple
therapy)
 Two nucleoside reverse transcriptase
inhibitors (NRTIs) combined with
either a protease inhibitor (PI) or a
non-nucleoside reverse transcriptase
inhibitor (NNRTI)
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Nucleoside reverse transcriptase inhibitors
(NRTIs)
Zidovudine
 Dideoxyinosine
 Dideoxycytidine
 Stavudine
 Lamivudine
 Etc.
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AZT
DDI
DDC
d4T
3TC
Non-Nucleoside reverse transcriptase
inhibitors (NNRTIs)
Delavirdine
 Efavirenz
 Nevirapine
 Copravirine
 Etc.
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DLV
EFV
NVP
CPV
Protease inhibitors (PIs)
Affect s posttranslational modification
(late stage) of HIV replication
 Ritonavir
RTV
 Indinavir
IDV
 Amprenavir
APV
 Etc.
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Entry inhibitors
(or fusion inhibitors)
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Block viral entry into cells
Fuzeon (enfuvirtide, T-20)
Goal of therapy
Maximal and durable suppression of
viral load in blood
 Restoration and/or preservation of
immunological function
 Reduction of HIV-related morbidity and
mortality
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Thailand
GPO-vir
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This is a generic drug combination of
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d4T (stavudine)
3TC (lamivudine)
NVP (nevirapine)
Side effects
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anemia : major (toxic to bone marrow and
blood cellls)
blood transfusion in severe case
leukopenia and granulocytopenia :
predispose to infections, fatigue, muscle pain,
rashes, nausea, diarrhea and headaches
hepatotoxicity, peripheral neuropathy and
pancreatitis
Side effects (oro-facial)
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Taste perversion
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Circumoral paresthesia
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Ritinovir (PI)
Amprenivir (PI)
Ritinovir (PI)
Stevens johnson syndrome (EM)
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Neviripine (NNRTI)
Amprenivir (PI)
Side effects (oro-facial)
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Stomatitis, oral ulceration
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Thrombocytopenia, anemia
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Indinavir (PI)
zidovudine (NRTI)
Parotid swelling (lipomatosis)
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Abacavir (NRTI)
Protease inhibitor
Xerostomia
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DDI
Protease inhibitors
Treatment planning
Current CD4 lymphocyte count
 Viral load
 Presence and status of opportunistic
infections
 Medications
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Dental Treatment
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Exposed to AIDS virus, HIV seropositive
but asymptomatic, ARC : CD4> 400
receive all indicated dental Tx.
Dental Treatment
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Symptomatic , early stage of AIDS
(CD4< 200) : increased susceptibility to
opportunistic infections
prophylactic drugs
receive most dental care
(after R/O neutropenia, thrombocytopenia)
Complex Tx. : prognosis of medical condition
Treatment planning
Medicated with drug, prophylactic for
opportunistic infection
allergic reaction, toxic drug
reaction, hepatotoxicity,
immunosuppression, anemia, serious
drug interaction
 Consultation, investigation (bleeding
time, WBC)
Dental management
severe thrombocytopenia
platelet replacement before surgery
 Prophylactic antibiotics : severe immune
neutropenia (< 500 cells/mm)
 In general , only urgent Tx. needs for
patient with advanced AIDS
Drug interaction
Acetaminophen :
caution with AZT (granulocytopenia,
anemia may be intensified)
 Aspirin : avoid in thrombocytopenia
 Antacids, phenytoin, cimetidine,
rifampin : avoid in ketoconazole
(altered absorption and metabolism)
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Cerebrovascular
accident
Stroke (CVA, apoplexy)
 Serious,
often fatal
 cerebrovascular disease
 Not fatal : some degree
debilitated in motor function,
speech or mentation
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Stroke : generic name
neurologic deficit
sudden interruption of
oxygenated bl to brain
focal necrosis of brain tissue
Interruption of blood supply :
Occlusive
- thrombosis of cerebral vessel
(65%-80%)
- cerebral embolism
 hemorrhage
- intracranial hemorrhage
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 Cerebrovascular
disease
 Atherosclerosis
(most common)
 hypertensive
vascular disease
 cardiac pathosis (MI, AF)
Factors (increased risk for stroke)
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Occurrence of TIAs
Hypertension
DM
Elevated blood lipid levels
Antiphospholipid antibodies
Black male
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Previous stroke
Cardiac abnormalities
Atherosclerosis
Elevated hematocrit level
Increasing age
Pathophysiology
 Pathologic
change from :
infarction
intracerebral hemorrhage
subarachnoidal hemorrhage
Infarction
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Cause : atherosclerotic thrombi or
emboli of cardiac origin
Extent of infarction :
site of occlusion, size of occluded vessel,
duration of occlusion, collateral circulation
Neurologic abnormalities :
artery involved
Intracerebral hemorrhage
 Cause
:
hypertensive atherosclerosis
microaneurysms of arterioles
Rupture
Subarachnoid hemorrhage
 Cause
:
rupture of a aneurysm at the
bifurcation of a major
cerebral artery
Sequelae and complications
Most serious :
death (38% - 47% within a month)
 Mortality rate related to type of stroke
80% : intracerebral hemorrhage
50% : subarachnoid hemorrhage
30% : occlusion of major vessel by
thrombus
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 Survive :
neurological deficit or disability of
varying degree and duration
10% recover with no impairment
40% mild residual ability
40% disabled + require special
service
10% require institutionalization
residual deficit:
size and location of infarct and hemorrhage
Deficit :
Unilateral paralysis
Numbness
Sensory impairment
Dysphasia
Blindness
Diplopia
Dizziness
Dysarthria
b
Residual
problem :
Difficulty in walking,
using the hands,
performing skilled act
or speaking
Clinical presentation
S/S
1. Transient ischemic attack (TIA)
2. Reversible ischemic neurological
deficit (RIND)
3. Stroke in evolution
4. Completed stroke
TIA
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Mini stroke
Cause : temporary disturbance in blood
supply to localized area of brain
Numbness of face, arm or leg one side
(hemiplegia), weakness, tingling, numbness,
speech disturbance < 10 min.
Major stroke proceded by 1 or 2 stroke within
several days
RIND
Neurologic deficit similar to TIA
 Not clear within 24 hr.
 Eventual recovery
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Stroke in evolution
Cause : occlusion or hemorrhage
 Deficit present for several hour
 Continue to worsen
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Stroke in evolution
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Signs:
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hemiplegia,
temporary loss of speech,
trouble in speaking or understanding
speech,
temporary dimness or loss of vision one
eye,
unexplained dizziness, unsteadiness or
suden fall
treatment
On respirator
 On Anticoaggulant
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Heparin
coumadin
Tx. of hypertension, DM, heart disease
 On aspirin
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Dental management
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Identification of risk factors
a. hypertension
b. DM
c. coronary atherosclerosis
d. elevated blood cholesterol or lipid level
e. cigarette smoking
f. TIA or previous stroke
g. increasing age
Encourage to control risk factors – refer
Dental management
 Hx.
of stroke
a. high risk – caution
b. urgent dental care only during
first 6 mo.
c. TIAs or RINDs – no elective
care
Dental management
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Hx. of stroke
d. anticoagulant drugs : bleeding problem
1. Aspirin : preTx. bleeding time < 20 min
2. Coumarin :
pre Tx. : PT < 2 times or INR < 3.0
if PT > 2 –2.5 times or INR > 3.0-3.5
consult to reduce dose
Dental management
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Hx. of stroke
d. anticoagulant drugs
3. Heparin IV – palliative emergency dental care
or discontinue 6-12 hr. prior to Sx. (with
physician’s approval ); restart after clot form
(6 hr. later)
Heparin (subcutaneous) – no changes required
4. Use measures to minimize hemorrhage
5. Hemostatic agents
Dental management
Short stress free, midmorning
appointment
 Monitor blood pressure
 minimum amount of LA with
vasoconstrictor
LA with 1:100,000 or 1:200,000 epi
(4 ml or less)
No epinephrine in retraction cord
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