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HIV Disease and AIDS

Worldwide, AIDS is the most common immunodeficiency disorder.Since the early 1980s, over 40 million people have been infected with HIV more than 12 million have died.These numbers continue to increase, especially in Third World countries.By 1994 it had become the leading cause of death among

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HIV Disease and AIDS

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    1. HIV Disease and AIDS Chapter 29

    2. Worldwide, AIDS is the most common immunodeficiency disorder. Since the early 1980s, over 40 million people have been infected with HIV – more than 12 million have died. These numbers continue to increase, especially in Third World countries. By 1994 it had become the leading cause of death among those 25-44 years of age in the U.S.

    3. Causative agent In the U.S. and most other parts of the world disease is caused by human immunodeficiency virus type 1 (HIV-1) Viruses characteristically infects mononuclear phagocytes HIV-2 is similar in structure to HIV-1 but is antigenically Distinct (has different envelope glycoproteins) Prominent cause of AIDS in parts of West Africa and India Produces a milder form of the disease, appears less virulent and has a longer latency period than HIV-1 Three main HIV-1 subtypes exist: M, N, and O Within subtype M are an additional 10 subtypes or clades (designated A through J)

    4. Virus Structure

    5. Pathogenesis Once inside the body, HIV virions are attracted to cells with CD4 on their surface Although numerous cell types can be infected, macrophages and Helper T-cells are the most important because of their role in the immune response

    7. Macrophages are initially infected (M-tropic): Viral gp120 binds to CD4 on the host cell surface After binding CD4, the shape of gp120 changes allowing it to also bind to coreceptor called CCR5 Binding to CCR5 is thought to help the virus cross the host cell membrane by triggering endocytosis

    9. After viral entry, DNA copies of RNA genome produced DNA copy integrates into host genome HIV does not lyse the macrophages that it infects but instead virions are released via exocytosis (budding) This is the basis for the long latency period HIV cycles through macrophages over a period of years HIV multiplies but no damage to the body occurs at this time

    10. HIV Genome

    12. Eventually, HIV alters the gene encoding gp120 so that it recognizes a “new” receptor. This altered form of gp120 binds to the co-receptor CXCR4 which resides on the surface of TH cells. Now HIV begins targeting TH cells (T-tropic). In contrast to macrophages, HIV production in TH cells causes their lysis. The TH cell population gradually begins to decrease.

    13. Symptoms Appear after incubation period of 6 days to 6 weeks Usually consist of fever, headache, sore throat, muscle aches, enlarged lymph nodes and generalized rash Symptoms constitute acute retroviral syndrome (ARS) Typically subside in 6 weeks Acute illness followed by asymptomatic period Period may end with persistent enlargement of lymph nodes Lymphadenopathy syndrome (LAS) Immunodeficiency symptoms include fever, weight loss, fatigue and diarrhea Referred to as AIDS-related complex (ARC)

    14. In nearly 80% of all cases immune system slowly loses ground to virus Peripheral CD4+ TH cell count steadily declines at a rate of about 50 cells/ľl/year AIDS symptoms usually appear when CD4+ TH cell count falls below 200 cells/ľl Atypical progression of disease occurs in roughly 10% of infected individuals Disease progresses rapidly to AIDS within a few months Another 5% - 10% do not experience a fall in CD4+ TH cells Maintain high levels of anti-HIV antibody and CD8+ Tc cells Disease progresses slowly 10-17% possibly AIDS free after 20 years

    15. Epidemiology Indiscriminate sexual intercourse major factor in spread Initially, promiscuous homosexual men were hit hardest Next most important mode of transmission is through blood and blood products By 1984 over 50% of hemophiliacs in U.S. were infected 10% - 20% of their sexual partners were HIV positive Intravenous drug users are at high risk Third most important mode of transmission is mother to infant One in 10 pregnant HIV-positive women will miscarry Of live-born infants, 15% - 40% will develop AIDS Breast feeding carries significant risk of mother-infant transmission

    17. Prevention and Treatment No approved vaccine Most people infected are unaware Virus on surfaces can be easily inactivated with commercially available high-level disinfectants and heat at 56°C or higher for 30 minutes Viruses in dried blood or pus may be more difficult to inactivate Knowledge of transmission greatest tool for control Use of condoms not 100% effective but have been shown to decrease transmission Avoidance of practices that favor HIV transmission

    18. Treatment directed at “cocktails” of drugs Combination of reverse transcriptase inhibitors and protease inhibitors HAART - highly active antiretroviral therapy Reverse transcriptase inhibitors fall into two categories Nucleoside reverse transcriptase inhibitors Zidovudine (AZT), stavudine (D4T) and lamivudine (3TC) Non-nucleoside reverse transcriptase inhibitors Nevirapine, efavirenz and delavirdine High cost ($) to therapy

    19. Protease inhibitors 6 in use Act late in HIV replication to prevent packaging of viral proteins HAART does not cure AIDS Viremia becomes undetectable in approximately 50% of cases Will reappear in absence of treatment Many strains fail to respond to HAART due to the development of resistance

    20. HIV vaccine prospects Currently no approved vaccines In theory vaccine could be used in two ways Prevention vaccine Immunize uninfected individuals against disease Therapeutic vaccine Boost immunity of those already infected

    21. Figure 29.8Figure 29.8

    22. Candidiasis

    23. Kaposi’s Sarcoma Unusual tumor arising from blood or lymphatic vessels in multiple locations Common in men of Mediterranean and Eastern European descent Not as a sign of immunodeficiency Tumor began to appear in young men with HIV 2,000 times higher than period before HIV So common among AIDS patients became AIDS-defining condition

    24. Human herpesvirus-8 (HHV-8) detected in sarcomas Virus infects endothelial cells that line blood and lymphatic vessels Persists mostly in latent form Presence of virus associated with two dramatic changes that result in tumor formation Cells assume spindle shape and proliferate Extensive formation of new blood vessels occurs

    25. Pneumocystosis Causative agent Pneumocystis carinii Tiny fungus belonging to phylum Ascomycota Formerly considered a protozoan Differs from many fungi in cell wall components Consequently resistant to many fungal medications

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