Download HIV/AIDS

HIV/AIDS
Human Immunodeficiency Virus
Acquired Immunodeficiency Syndrome
1
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

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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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