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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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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. Kaposis 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