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HIV

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.

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HIV

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  1. HIV

  2. 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

  3. Pathophysiology Transmission : - sexual - nonsexual

  4. Categorization of HIV exposures • Group 1 HIV antibody positive – asymptomatic • Group 2 ARC, CD4 < 400 symptoms (fever, malaise, lymphadenopathy, diarrhea), opportunistic infections

  5. Categorization of HIV exposures • Group 3 AIDS; CD4 < 200 Kaposi’s sarcoma, lymphoma, pneumonia, cervical carcinoma, etc.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Laboratory test • Status and potential risk of surgery • Viral load • CD4 lymphocyte count

  12. 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

  13. 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

  14. 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,

  15. Opportunistic infection • Toxoplasmosis • Protozoa • Infection of CNS • Symptoms : neurologic headaches, dizziness, seizures

  16. Opportunistic infection • Cryptosporidiosis • Protozoa • Affect GI tract Nausea, vomiting, diarrhea, malaise, fever, weight loss

  17. Opportunistic infection • Candidiasis • Oral and systemic • Infect mucous membrane : mouth, vagina, esophagus, GI tract, skin • Systemic Tx. Fluconazole or ketoconazole

  18. 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

  19. Opportunistic infection • Tuberculosis • Mycobacterium tubercullosis • S/S : lymphadenopathy, cough, fever weight loss, diarrhea, night sweats, malaise • Skin test • Tx : Isoniazid (INH), Rifampin, ethambutol, streptomycin

  20. Opportunistic infection • Tuberculosis • Multiantibioticresistant form of TB • Mycobacterium avium • Mycobacterium intracellulare • Tx. : ciprofloxacin, amikacin sulfate, ethambutol

  21. Opportunistic infection • Cytomegalovirus • 90% of HIV • Oral cavity : deep, non-healing ulcerations • Retinitis • Esophagitis • Colitis • Tx. : Ganciclovir

  22. Opportunistic infection • Herpes simplex/ herpes zoster • Infect epithelial tissue and nerve ending • Symptoms: painful inflammatory blisters follow a sensory nerve tract • Tx./prophylaxis : acyclovir

  23. Opportunistic infection • Epstein-Barr virus • Associated with oral hairy leukoplakia in HIV/AIDS • Acyclovir or ganciclovir

  24. Opportunistic infection • Human papillomavirus • Oral cavity • Clinical : oral warts • Tx. excision

  25. 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)

  26. Nucleoside reverse transcriptase inhibitors(NRTIs) • Zidovudine AZT • Dideoxyinosine DDI • Dideoxycytidine DDC • Stavudine d4T • Lamivudine 3TC • Etc.

  27. Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) • Delavirdine DLV • Efavirenz EFV • Nevirapine NVP • Copravirine CPV • Etc.

  28. Protease inhibitors (PIs) • Affect s posttranslational modification (late stage) of HIV replication • Ritonavir RTV • Indinavir IDV • Amprenavir APV • Etc.

  29. Entry inhibitors (or fusion inhibitors) • Block viral entry into cells Fuzeon (enfuvirtide, T-20)

  30. 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

  31. Thailand GPO-vir • This is a generic drug combination of • d4T (stavudine) • 3TC (lamivudine) • NVP (nevirapine)

  32. 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

  33. Side effects (oro-facial) • Taste perversion • Ritinovir (PI) • Circumoral paresthesia • Amprenivir (PI) • Ritinovir (PI) • Stevens johnson syndrome (EM) • Neviripine (NNRTI) • Amprenivir (PI)

  34. Side effects (oro-facial) • Stomatitis, oral ulceration • Abacavir (NRTI) • Thrombocytopenia, anemia • Indinavir (PI) • zidovudine (NRTI) • Parotid swelling (lipomatosis) • Protease inhibitor • Xerostomia • DDI • Protease inhibitors

  35. Treatment planning • Current CD4 lymphocyte count • Viral load • Presence and status of opportunistic infections • Medications

  36. Dental Treatment • Exposed to AIDS virus, HIV seropositive but asymptomatic, ARC : CD4> 400 receive all indicated dental Tx.

  37. 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

  38. 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)

  39. 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

  40. 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)

  41. Cerebrovascular accident

  42. Stroke (CVA, apoplexy) • Serious, often fatal • cerebrovascular disease • Not fatal : some degree debilitated in motor function, speech or mentation

  43. Stroke : generic name neurologic deficit sudden interruption of oxygenated bl to brain focal necrosis of brain tissue

  44. Interruption of blood supply : • Occlusive - thrombosis of cerebral vessel (65%-80%) - cerebral embolism • hemorrhage - intracranial hemorrhage

  45. Cerebrovascular disease • Atherosclerosis (most common) • hypertensive vascular disease • cardiac pathosis (MI, AF)

  46. 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

  47. Pathophysiology • Pathologic change from : infarction intracerebral hemorrhage subarachnoidal hemorrhage

  48. 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

  49. Intracerebral hemorrhage • Cause : hypertensive atherosclerosis microaneurysms of arterioles Rupture

  50. Subarachnoid hemorrhage • Cause : rupture of a aneurysm at the bifurcation of a major cerebral artery

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