Transcript HIV/AIDS
HIV/AIDS
Human Immunodeficiency Virus
Acquired Immunodeficiency Syndrome
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The Beginning
Don’t really know where it came from.
Doesn’t matter for this class except for historical
purposes.
Is important for gaining insight into how the
virus evolved.
– Is it new or old?
– If new, may have lots of new strains.
Thus, new developed vaccines will not work in 10-20 years.
– If old, part of the global system.
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Causes of AIDS
Major Hypotheses
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AIDS is Not Caused by HIV.
Also reject that AIDS is a unique medical
condition.
Is a minority view.
Advocates
ACT – UP
Alive and Well
Duesberg
Mbeki
South Africa President
One U.S. Congressional representative
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AIDS is Caused by HIV
Satisfies Koch’s Postulates (1890)
– Causative agent is found in all cases of the
disease.
– It can be isolated from the host and be grown
in a pure culture.
– Must reproduce the original disease when
introduced into a susceptible host.
– Must be found in the experimental host so
infected.
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Other Significant Evidence
Is the one common denominator within a
range of populations.
Has been identified by electron
microscopy.
Antibodies, viral antigens, and HIV RNA
have been found in HIV-Positive and AIDS
patients.
Many others
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More Origins of HIV
Unidentified Flying Objects (UFO’s) coming from space
Is a biological weapon designed to kill non-whites.
Came from domestic cats. (Feline AIDS is similar to
Human AIDS)
HIV Contaminated _______ vaccines.
Polio
Smallpox
Tetanus
Hepatitis
African Green Monkey
African People
African Cattle, Pigs, Sheep
CIA and other spy agencies
Biological Weapons Labs
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Other Origin Ideas
Hirsch et al. (1995)
Virus came from Sooty Mangabey (Ash Colored Monkey)
– May have infected humans 20-30 years ago
– Virus evolved into HIV-2
Molecularly cloned the virus and sequenced the
DNA
– Constructed a evolutionary tree of known primate
immunodeficiency viruses
– SIVsm appeared very similar to HIV-2, but not HIV-1
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Osterhaus
Contends all human viral diseases have an
animal origin that naturally cross into
humans.
HIV virus remained obscure for a long
time before changing into a lethal disease.
Evidence
– Thin’s Disease reported by peace corps
workers.
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Earliest Known Case
Based on genetic analysis from a blood
sample taken from the Congo in 1959.
Wolinsky
1924 - 1946
Korber
1910 - 1950
Salemi et al 1675 – 1900
– HIV in humans about 1920’s – 1930’s
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Current Theory
Hahn et al. (1999, 2000)
Simian virus closely related to HIV jumped from chimps
to humans .
Virus then mutated into its current form.
Evidence
– Genes from all four SIVcpz isolates cluster to their subspecies or
origin
Pan Troglodytes Troglodytes - West Africa
Pan Trogldytes Scheinfurthii - East Africa
– All known HIV-1 strains cluster with W. Africa Chimp viruses
– Evidence of genetic recombination among SIVcpz strains of the
Troglodytes lineage.
Newer evidence indicates multiple jumpings – different
strains
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Example
HIV Strains have 11 distinct subtypes
– A-K
– Subtype B is dominant in US and Europe
– Subtype D is dominant in Africa
Virus mutates rapidly.
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United States
Virus has been in the US since mid. 1970’s.
– 1979-1981
– Physicians in New York and Los Angeles began
reporting particular diseases in Gay Males.
– Including:
Rare Pneumonias
Cancers
Other diseases
– Diseases were not usually found in people with
healthy immune systems.
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1982
Public Health begins using term Acquired
Immunodeficiency Syndrome (AIDS) to describe
opportunistic infections in previously healthy
men.
– Including
Kaposi’s Sarcoma
Pneumocystis Carni Pneumonia
Surveillance of AIDS begins
Diagnosis of cellular immune deficiency
Absence of an underlying cause
Reduced resistance to the disease
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HIV Surveillance
Definition modified in 1983
Required to be reported to CDC
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1983
First cases of AIDS in heterosexuals are documented.
Virus is isolated by various labs.
Named
– HTLV-III (Human T-Lymphotrophic Virus-III)
(Gallo)
– LAV
(Lymphadenopathy Associated Virus)
(Luc Montagnier Mont-Tan-Ya)
– ARV
(AIDS – Related Virus)
Ultimately named
– HIV
(Human Immunodeficiency Virus)
(Sub-committee of the Committee on the Taxonomy of
Viruses
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1985
Second type of HIV discovered
– HIV-2
Related to SIV
Not as related to HIV-1
Does not seem as harmful as HIV-1
Reproduces slower than HIV-1
Screening tests become available
Tests of stored blood samples indicate HIV was
being transmitted in US and Europe in mid to
late 1970’s.
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Early Definitions of AIDS
1981-93
Many definitions of AIDS
Problem
– Social Security Administration (SSA)
– Used AIDS definition to determine disability
Symptoms were based on opportunistic infections
in men.
– Result
65% of women were excluded
Other problems too
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1993
New definition of AIDS
Emphasized the importance of T4 lymphocyte
counts.
Added other diseases
System becomes simpler
Also allowed one to become diagnosed with
AIDS but remain symptom-free of diseases.
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1987
First case of HIV-2 in the U.S.
First Anti - HIV drugs become available
– Zidovudine (AZT)
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1988
Protease Inhibitors are identified.
Have problems with
– Absorption
– Have rapid liver metabolism
– Insolubility
Result – More development and clinical
trials.
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1992
Protease Inhibitors (PI) become more developed
First - Saquinavir Mesylate (Invirase)
–
–
–
–
Was used in combination with other drugs
Minimal clinical trial data
Had poor absorption
Was the least potent of other PI’s that came on the
market later.
Second – Ritonavir (Norvir)
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More Protease Inhibitors are Developed
Saquinavir
(Fortovase)
Indinavir
(Crixivan)
Nelfinavir
Amprenavir
ABT – 378
(Viracept)
(Agenerase)
(Kaletra)
Problem
– More easily absorbed by the body
– Most often used
– Drugs are expensive $450-$700/month
– = $5,400 - $8,400/yr
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2000
Drug Combinations (Cocktails)
Use multiple combinations of drugs
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2001
Negotiations to reduce costs
Generics are developed by outside
countries despite patent laws.
– Is a major problem
Costs go down
Drug companies reevaluate staying in the
HIV drug market
When do you use (early vs. later)
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Present
HIV continues to mutate
– Currently getting HIV resistance to drugs
People are returning to previous lifestyles
– Drugs are effective at helping people
– Can work
– Enjoy life
People do not take drugs so they effectively block the
virus
– Monotherapy
– Also stop drugs when they do not have
money
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People
stop taking drugs when
they are feeling better
People who are infected are
having sex with other infected
individuals.
Result
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1. Drug Resistance
30% of newly infected individuals have
viral forms that resistant to at least one
drug.
Drug resistant strains are becoming more
powerful
Result – Salvage therapy
– Give everything you can
– 30-50% of HIV infected persons are in such
therapy.
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2. New Strains
Are more powerful than previous strains
Cause individuals who are doing well on
drug cocktails to become ill again
Has caused us to reevaluate the issues of
vaccines
Is going to become a real problem
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Issues
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HIV is a Unique Disease
Affects mostly young and middle aged
adults.
Are sexually active
Are in their prime productive and
reproductive years
Impact is demographic, economic,
political, and social.
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Other Issues
Have forgotten the past
STD rates (e.g., syphilis) are increasing
again
1999-2002 number of males with new HIV
infections increased 7.3% (CDC, 2003
– Among MSMs increased 17%
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Is Similar to Other Epidemics and
Pandemics
– Measles from 430bc
– Malaria 1847-1875
– Influenza 1918-1919
– Smallpox
– HIV/AIDS deaths
– HIV/AIDS cases
– TB since 1770
– SARS
Millions
20 million +
21,640,000
Hundreds of Mill.
27,000,000
41,000,000
1 billion
?????
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Since 1970
Many New Diseases
Lyme Disease
Legionnaires Disease
Toxic Shock Syndrome
HIV
Three new Herpes viruses (HHV 6,7,8)
Hantavirus
Ebola
Bovine Spongiform
Rotaviruses Encephalopathy
Dengue Hemorrhagic Fever
Hepatitis C 170 million people are infected
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Conclusion
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HIV Is A Preventable Disease
To stop the disease, must change the
behavior.
Is a system of numbers.
– More people in a population that have it,
– The greater the likelihood you will get it.
1/100 vs. 10/100 vs. 25/100 vs. 50/100
1/100
1/10
1/4
1/2
1%
10%
25%
50%
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