HIVAIDS Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome 1

HIV/AIDS Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome 1

The Beginning Don’t really know where it came from. n Doesn’t matter for this class except for historical purposes. n Is important for gaining insight into how the virus evolved. n – 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. 2

Causes of AIDS Major Hypotheses 3

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 4

AIDS is Caused by HIV n 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. 5

Other Significant Evidence n Is the one common denominator within a range of populations. n Has been identified by electron microscopy. n Antibodies, viral antigens, and HIV RNA have been found in HIV-Positive and AIDS patients. n Many others 6

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) n HIV Contaminated _______ vaccines. n n n Polio Smallpox Tetanus Hepatitis n n n African Green Monkey African People African Cattle, Pigs, Sheep CIA and other spy agencies Biological Weapons Labs 7

Other Origin Ideas n Hirsch et al. (1995) n Virus came from Sooty Mangabey (Ash Colored Monkey) – May have infected humans 20 -30 years ago – Virus evolved into HIV-2 n 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 8

Osterhaus n Contends all human viral diseases have an animal origin that naturally cross into humans. n HIV virus remained obscure for a long time before changing into a lethal disease. n Evidence – Thin’s Disease reported by peace corps workers. 9

Earliest Known Case n Based on genetic analysis from a blood sample taken from the Congo in 1959. n Wolinsky 1924 - 1946 n Korber 1910 - 1950 n Salemi et al 1675 – 1900 – HIV in humans about 1920’s – 1930’s 10

Current Theory Hahn et al. (1999, 2000) n Simian virus closely related to HIV jumped from chimps to humans. n Virus then mutated into its current form. n Evidence n – Genes from all four SIVcpz isolates cluster to their subspecies or origin § Pan 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. n Newer evidence indicates multiple jumpings – different strains 11

Example n HIV Strains have 11 distinct subtypes – – – n A-K Subtype B is dominant in US and Europe Subtype D is dominant in Africa Virus mutates rapidly. 12

United States n 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. 13

1982 n Public Health begins using term Acquired Immunodeficiency Syndrome (AIDS) to describe opportunistic infections in previously healthy men. – Including § Kaposi’s Sarcoma § Pneumocystis Carni Pneumonia n Surveillance of AIDS begins Diagnosis of cellular immune deficiency Absence of an underlying cause Reduced resistance to the disease 14

HIV Surveillance n Definition modified in 1983 n Required to be reported to CDC 15

1983 First cases of AIDS in heterosexuals are documented. n Virus is isolated by various labs. n Named n – 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 16

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 n Screening tests become available n Tests of stored blood samples indicate HIV was being transmitted in US and Europe in mid to late 1970’s. n 17

Early Definitions of AIDS 1981 -93 n Many definitions of AIDS n 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 18

1993 n n n New definition of AIDS Emphasized the importance of T 4 lymphocyte counts. Added other diseases System becomes simpler Also allowed one to become diagnosed with AIDS but remain symptom-free of diseases. 19

1987 n First case of HIV-2 in the U. S. n First Anti - HIV drugs become available – Zidovudine (AZT) 20

1988 n Protease Inhibitors are identified. n Have problems with – Absorption – Have rapid liver metabolism – Insolubility n Result – More development and clinical trials. 21

1992 Protease Inhibitors (PI) become more developed n First - Saquinavir Mesylate (Invirase) n – – n 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) 22

More Protease Inhibitors are Developed n Saquinavir (Fortovase) n Indinavir (Crixivan) n n n Nelfinavir Amprenavir ABT – 378 (Viracept) (Agenerase) (Kaletra) n Problem – More easily absorbed by the body – Most often used – Drugs are expensive $450 -$700/month – = $5, 400 - $8, 400/yr 23

2000 n Drug Combinations (Cocktails) n Use multiple combinations of drugs 24

2001 n Negotiations to reduce costs n Generics are developed by outside countries despite patent laws. – Is a major problem n Costs go down n Drug companies reevaluate staying in the HIV drug market n When do you use (early vs. later) 25

Present n HIV continues to mutate – Currently getting HIV resistance to drugs n People are returning to previous lifestyles – Drugs are effective at helping people – Can work – Enjoy life n People do not take drugs so they effectively block the virus – Monotherapy – Also stop drugs when they do not have money 26

n People stop taking drugs when they are feeling better n People who are infected are having sex with other infected individuals. §Result 27

1. Drug Resistance n 30% of newly infected individuals have viral forms that resistant to at least one drug. n Drug resistant strains are becoming more powerful n Result – Salvage therapy – Give everything you can – 30 -50% of HIV infected persons are in such therapy. 28

2. New Strains n Are more powerful than previous strains n Cause individuals who are doing well on drug cocktails to become ill again n Has caused us to reevaluate the issues of vaccines n Is going to become a real problem 29

Issues 30

HIV is a Unique Disease n Affects mostly young and middle aged adults. n Are sexually active n Are in their prime productive and reproductive years n Impact is demographic, economic, political, and social. 31

Other Issues n Have forgotten the past n STD rates (e. g. , syphilis) are increasing again n 1999 -2002 number of males with new HIV infections increased 7. 3% (CDC, 2003 – Among MSMs increased 17% 32

Is Similar to Other Epidemics and Pandemics – Measles from 430 bc – 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 41, 000 1 billion ? ? ? 33

Since 1970 Many New Diseases n n n 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 34

Conclusion 35

HIV Is A Preventable Disease n To stop the disease, must change the behavior. n 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 1/10 1/4 1/2 1% 10% 25% 50% 36