HIVHIV

The Human immunodeficiency virus

RetrovirusRNA virusProtein coat (HIV antigens)Reverse transcriptase turn RNA into DNAHIV integrase incorporates viral DNA into host genomeTranscribed by host/viral enzymesViral 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

Categorization of HIV exposures

Group 3 AIDS; CD4 < 200 Kaposi’s sarcoma, lymphoma, pneumonia, cervical carcinoma, etc.

Signs and symptoms

Initial exposure or infection Flulike symptoms-fever, weakness, 10

to 14 days Asymptomatic stage

serologic evidence of infection no signs or symptoms

Signs and symptoms

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

Signs and symptoms

Advanced symptomatic stage 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 :

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

Laboratory test

Status and potential risk of surgery Viral load CD4 lymphocyte count

Laboratory test

Viral load 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

Laboratory test

CD4 lymphocyte Degree of immunologic destruction

AIDS : low lymphocyte count and depressed CD4 T-cells CD4 : CD8 ratio of 1:0 or less

Opportunistic infection

Pneumocystis carinii pneumonia (PCP) Protozoan parasite Invade lungs (rarely LN) Symptoms : fever, cough, difficulty

breathing, weight loss, night sweats, fatigue

Prophylaxis : TMP-SMX,

Opportunistic infection

Toxoplasmosis Protozoa Infection of CNS Symptoms : neurologic headaches, dizziness, seizures

Opportunistic infection

Cryptosporidiosis Protozoa Affect GI tract Nausea, vomiting, diarrhea, malaise,

fever, weight loss

Opportunistic infection

Candidiasis Oral and systemic Infect mucous membrane : mouth,

vagina, esophagus, GI tract, skin Systemic Tx. Fluconazole or

ketoconazole

Opportunistic infection

Cryptococcus and histoplasma 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

Tuberculosis Mycobacterium tubercullosis S/S : lymphadenopathy, cough, fever

weight loss, diarrhea, night sweats, malaise

Skin test Tx : Isoniazid (INH), Rifampin,

ethambutol, streptomycin

Opportunistic infection

Tuberculosis Multiantibioticresistant form of TB Mycobacterium avium Mycobacterium intracellulare

Tx. : ciprofloxacin, amikacin sulfate, ethambutol

Opportunistic infection

Cytomegalovirus 90% of HIV Oral cavity : deep, non-healing

ulcerations Retinitis Esophagitis Colitis

Tx. : Ganciclovir

Opportunistic infection

Herpes simplex/ herpes zoster Infect epithelial tissue and nerve

ending Symptoms: painful inflammatory

blisters follow a sensory nerve

tract Tx./prophylaxis : acyclovir

Opportunistic infection

Epstein-Barr virus Associated with oral hairy leukoplakia

in HIV/AIDS Acyclovir or ganciclovir

Opportunistic infection

Human papillomavirus 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)

Nucleoside reverse transcriptase inhibitors(NRTIs)

Zidovudine AZT Dideoxyinosine DDI Dideoxycytidine DDC Stavudine d4T Lamivudine 3TC Etc.

Non-Nucleoside reverse transcriptase inhibitors (NNRTIs)

Delavirdine DLV Efavirenz EFV Nevirapine NVP Copravirine CPV Etc.

Protease inhibitors (PIs)

Affect s posttranslational modification (late stage) of HIV replication

Ritonavir RTV Indinavir IDV Amprenavir APV Etc.

Entry inhibitors (or fusion inhibitors)

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

Thailand

GPO-vir This is a generic drug combination

of d4T (stavudine) 3TC (lamivudine) NVP (nevirapine)

Side effects

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)

Taste perversion Ritinovir (PI)

Circumoral paresthesia Amprenivir (PI) Ritinovir (PI)

Stevens johnson syndrome (EM) Neviripine (NNRTI) Amprenivir (PI)

Side effects (oro-facial)

Stomatitis, oral ulceration Abacavir (NRTI)

Thrombocytopenia, anemia Indinavir (PI) zidovudine (NRTI)

Parotid swelling (lipomatosis) Protease inhibitor

Xerostomia DDI Protease inhibitors

Treatment planning

Current CD4 lymphocyte count Viral load Presence and status of

opportunistic infections Medications

Dental Treatment

Exposed to AIDS virus, HIV seropositive but asymptomatic, ARC : CD4> 400

receive all indicated dental Tx.

Dental Treatment

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)

Cerebrovascular Cerebrovascular accidentaccident

Stroke (CVA, apoplexy)

Serious, often fatalcerebrovascular diseaseNot fatal : some degree debilitated in motor function, speech or mentation

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

Cerebrovascular disease

Atherosclerosis

(most common)hypertensive vascular disease

cardiac pathosis (MI, AF)

Factors (increased risk for Factors (increased risk for stroke)stroke)

Occurrence of TIAs Hypertension DM Elevated blood lipid

levels Antiphospholipid

antibodies Black male

Previous stroke Cardiac abnormalities Atherosclerosis Elevated hematocrit level Increasing age

Pathophysiology

Pathologic change from : infarction intracerebral hemorrhage subarachnoidal

hemorrhage

Infarction

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

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

hemorrhageDeficit : Unilateral paralysis Numbness Sensory impairment Dysphasia Blindness Diplopia Dizziness Dysarthria

bResidual problem : Difficulty in walking, using the hands, performing skilled act or speaking

Clinical presentationClinical presentation

S/S 1. Transient ischemic attack (TIA) 2. Reversible ischemic

neurological deficit (RIND) 3. Stroke in evolution 4. Completed stroke

TIA

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

Stroke in evolution

Cause : occlusion or hemorrhage Deficit present for several hour Continue to worsen

Stroke in evolution

Signs: 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

Heparin coumadin

Tx. of hypertension, DM, heart disease

On aspirin

Dental management 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 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 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