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 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 Dideoxyinosine Dideoxycytidine Stavudine Lamivudine Etc. AZT DDI DDC d4T 3TC Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) Delavirdine Efavirenz Nevirapine Copravirine Etc. DLV EFV NVP CPV 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 Circumoral paresthesia Ritinovir (PI) Amprenivir (PI) Ritinovir (PI) Stevens johnson syndrome (EM) Neviripine (NNRTI) Amprenivir (PI) Side effects (oro-facial) Stomatitis, oral ulceration Thrombocytopenia, anemia Indinavir (PI) zidovudine (NRTI) Parotid swelling (lipomatosis) Abacavir (NRTI) 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 accident Stroke (CVA, apoplexy) Serious, often fatal cerebrovascular disease Not 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 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 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 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