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Terminology

HIV Human Immunodeficiency Virus. AIDS Acquired Immune Deficiency Syndrome. Terminology. Classification of HIV. 2 types of HIV: HIV - 1 HIV - 2. Genetic forms of HIV - 1. some phylogenetic groups :

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Terminology

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  1. HIV Human Immunodeficiency Virus AIDS Acquired Immune Deficiency Syndrome Terminology

  2. Classification of HIV 2 types of HIV: HIV - 1 HIV - 2

  3. Genetic forms of HIV - 1 somephylogeneticgroups: M (main) 9 subtypes (A – D, F – H, J i K) O (outlier) (rare) N (novel) (rare) P CRF (CirculatingRecombinantForms)

  4. Replication cycle of HIV - Viralgp 120 binds to CD4 receptor of a lymphocyte • Coreceptors for entry: CCR5 or CXCR4 arehelpful • Fusion of HIV withcellularmembrane of lymphocyteoccurs – virusentersthecell • Viral RNA isconverted (transcripted) into DNA by reversetranscriptase • HIV DNA (provirus) integrateswith DNA of a lymphocyte • RNA copies of a provirusaremade (mRNA) – transcription • mRNAistransported to thecytoplasm and makesthe host cellproduce long chains of viral protein (translation) • HIV core protein and genomic RNA gatherinsidethecell and immatureviralparticles form and bud offfromthecell • Chain of viral protein iscutintopieces by protease. Thatresultsin forming infectiousviralparticles.

  5. Targets of HIV Therapy Integrase Inhibitors Nucleus Entry Inhibitors: Fusion, CD4, CCR5 CXCR4 RNA Protease DNA Reverse transcriptase HIV CD4+ T-Cell Protease inhibitors Reverse transcriptase inhibitors: NRTI (nucleosides, nucleotides) NNRTI

  6. Global estimates for adults and children, 2008 • People living with HIV33.4 million[31.1 – 35.8 million] • New HIV infections in 20082.7 million [ 2.4 – 3.0 million] • Deaths due to AIDS in 20082.0 million[1.7 – 2.4 million]

  7. Adults and children estimated to be living with HIV, 2008 Eastern Europe & Central Asia 1.5 million [1.4 – 1.7 million] Western & Central Europe 850 000 [710 000 – 970 000] North America 1.4 million [1.2 – 1.6 million] East Asia 850 000 [700 000 – 1.0 million] Middle East&North Africa 310 000 [250 000 – 380 000] Caribbean 240 000 [220 000 – 260 000] South & South-East Asia 3.8 million [3.4 – 4.3 million] Sub-Saharan Africa 22.4 million [20.8 – 24.1 million] Latin America 2.0 million [1.8 – 2.2 million] Oceania 59 000 [51 000 – 68 000] Total: 33.4 million (31.1 – 35.8 million)

  8. HIV infection in the three geographical areas and EU/EEA, WHO European Region, 2004–10 Data not reported or not available from Austria, Russia, Monaco. Source: ECDC/WHO. HIV/AIDS Surveillance in Europe, 2010

  9. HIV infections diagnosed in 2010 per 100 000 population: all cases Source: ECDC/WHO. HIV/AIDS Surveillance in Europe, 2010

  10. HIV infections, 2004–10: transmission groups in WHO European Region, East Source: ECDC/WHO. HIV/AIDS Surveillance in Europe, 2010

  11. HIV infections, 2004–09: transmission groups in WHO European Region, Centre Source: ECDC/WHO. HIV/AIDS Surveillance in Europe, 2010

  12. Distribution of three most common AIDS indicative diseases by transmission group, WHO European Region, 2010 *pulmonary in adults and adolescents

  13. HIV – routes of transmission • Contaminated blood products • Sexual intercourse • Mother- to- child (vertical route)

  14. HIV – routes of transmission Contaminated blood products -blood transfusion -skin penetrating procedures -contact of contaminated body fluid with mucose membrane or non intact skin

  15. Risk of HIV transmission after single exposure to contaminated blood • Percutaneus - needlestick in HCW 0,32% - sharing needles by IDU 0,67% • Mucous membranes 0,09% • Non-intact skin - lower risk (several cases reported) • Exposure to other contaminated fluids - still lower risk

  16. Circumstances increasing the risk of transmission • Deep penetration 16,1% • Blood visible on the tool 5,2% • Needle just withdrawn from the vein 5,1% • End-stage AIDS 6,4% Applying retrovir in post exposure prophylaxis decreases the risk by 80%

  17. HIV – routes of transmission Sexual intercourse Risk about 0,5 %

  18. Risk of pathogen transmission resulting from a single sexual contact with infected person HIV 0,5% Gonorrhea 22-25%

  19. HIV – routes of transmission Mother–to-child transmission (vertical transmission) Frequency 30% - 1% ( in Africa 40% )

  20. Vertical transmission of HIV • Transmissionrateisrelated to HIV infectionstage and viralloadinthemother • Mainroutes: - delivery - breastfeeding - transplacental

  21. Infectious body fluids in HIV positive individual • Blood and its derivates • Seminal fluid • Discharge from genital tract - vaginal exsudate - cervical mucus • Human milk • Cerebro-spinal fluid • Synovial fluid, amniotic fluid, pericardial fluid, pleural fluid, peritoneal fluid. • Any fluid contaminated with blood • Samples of tissues, transplants • Concentrate of virus used in research laboratories

  22. Cells with CD4 receptor on surface • T lymphocytes (T helper) • T-cell precursors in the bone marrow and thymus • Monocytes/macrophages • Dendritic cells (in the lymphatic organs, gut, genitourinary tract, submucosal tissue) • Microglia cells (in the central nervous system) • Retinal cells Co-receptors: CCR5, CXCR4

  23. Pathogenesis • HIV enters the susceptible cells, replicates and spreads in the body of the host. • Cell - mediated immunity is activated and kills the virus particles. • Specific antibodies are produces to fight the infection (humoral immunity). • Some viruses reach the reservoirs ( eg.lymph nodes, brain, urogenitary tract) and are safe from antibodies and killer cells. • The rate of replication gets established (set point). • HIV destroys T-lymphocytes (lysis, apoptosis), new lymphocytes are being produced (balance). • T-lymphocytes count declines (immunodeficiency)

  24. Surface pathogens • Skin Streptococci, staphylococci • Mucose membranes Streptococci, staphylococci, candida sp., anaerobic bacteria (fusobacterium) Pulmonary alveoli – cryptococci, Pneumocystis carinii GI tract – Escherichia coli Saprofites are useful in immunocompetent patient.

  25. Latent infectionsEarly colonization of the body

  26. Sequelae of lymphocytes CD4 deficiency • Activation of surface pathogens Candida albicans Cryptococcus neoformans Pneumocystis carinii • Reactivation of latent infections Herpes simplex virus (HSV) Varicella-zoster virus (VZV) - shingles Cytomegalovirus (CMV) Toxoplasma Epstein – Barr virus (EBV) • Developing of neoplasms Kaposi`s sarcoma Non-Hodgkin`s lymphoma Cervical carcinoma • Insufficient serologic response to new antigens New infection – serologic diagnostic tests unreliable, Vaccination – poor response (if any)

  27. HIV / AIDS HIV infection ↓ Depletion of CD4 lymphocytes ↓ Immunodeficiency ↓ Opportunistic infections (reactivation) Specific tumors

  28. HIV testing Standard serologic test: - ELISA repeatedly reactive ( 2 different samples) + - Western-Blot reactive = HIV serology positive Window period 2-6 weeks (rarely up to 3 months) (Time delay from infection to positive test) Viral detection: (newborns, occupational exposures) - HIV RNA (PCR) - p-24 antigen - culture of the virus

  29. False negative ELISA test • Diagnosticwindow 14 days – 3 months (6 months) • Seroreversionintheendstage of infection • Agammaglobulinaemia

  30. False negative ELISA test • Diagnosticwindow 14 days – 3 months (6 months) • Seroreversionintheendstage of infection • Agammaglobulinaemia

  31. False positive ELISA test • Cross reactiveantibodies - collagenoses - autoimmunologicdisorders - liverdiseases - multiplesclerosis - endstagekidneydisease • Vaccinationagainst HIV 68% of personshaveantibodies

  32. Rapid detection testing (needs confirmation with ELISA and WB) Clinical use: - in labor (no prenatal HIV test) - in patient who is a source of needlestick injury to health care provider - evaluation of acutely ill patient with possible PCP

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