HIV/AIDS

1
HIV/AIDS

• Human Immunodeficiency Virus
• Acquired Immunodeficiency Syndrome

2
The Beginning

• Dont really know where it came from.
• Doesnt 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.

3
Causes of AIDSMajor Hypotheses
4
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

5
AIDS is Caused by HIV

• Satisfies Kochs 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.

6
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

7
More Origins of HIV

• Unidentified Flying Objects (UFOs) 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

8
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

9
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
• Thins Disease reported by peace corps workers.

10
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 1920s 1930s

11
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

12
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.

13
United States

• Virus has been in the US since mid. 1970s.
• 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.

14
1982

• Public Health begins using term Acquired
  Immunodeficiency Syndrome (AIDS) to describe
  opportunistic infections in previously healthy
  men.
• Including
• Kaposis Sarcoma
• Pneumocystis Carni Pneumonia
• Surveillance of AIDS begins
• Diagnosis of cellular immune deficiency
• Absence of an underlying cause
• Reduced resistance to the disease

15
HIV Surveillance

• Definition modified in 1983
• Required to be reported to CDC

16
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

17
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
  1970s.

18
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

19
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.

20
1987

• First case of HIV-2 in the U.S.
• First Anti - HIV drugs become available
• Zidovudine (AZT)

21
1988

• Protease Inhibitors are identified.
• Have problems with
• Absorption
• Have rapid liver metabolism
• Insolubility
• Result More development and clinical trials.

22
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 PIs that came on
  the market later.
• Second Ritonavir (Norvir)

23
More Protease Inhibitors are Developed

• Saquinavir (Fortovase)
• More easily absorbed by the body
• Indinavir (Crixivan)
• Most often used
• Nelfinavir (Viracept)
• Amprenavir (Agenerase)
• ABT 378 (Kaletra)
• Problem
• Drugs are expensive 450-700/month
• 5,400 - 8,400/yr

24
2000

• Drug Combinations (Cocktails)
• Use multiple combinations of drugs

25
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)

26
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

27

• People stop taking drugs when they are feeling
  better
• People who are infected are having sex with other
  infected individuals.
• Result

28
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.

29
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

30
Issues
31
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.

32
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

33
Is Similar to Other Epidemics and Pandemics

• Measles from 430bc Millions
• Malaria 1847-1875 20 million
• Influenza 1918-1919 21,640,000
• Smallpox Hundreds of Mill.
• HIV/AIDS deaths 27,000,000
• HIV/AIDS cases 41,000,000
• TB since 1770 1 billion
• SARS ?????

34
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

35
Conclusion
36
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