Human Immunodeficiency Virus Kyle Kuhn Gerard Jenkins and

Human Immunodeficiency Virus Kyle Kuhn, Gerard Jenkins and Agnes Kazior March 11, 2003

What is HIV? • Any of several retroviruses that infect and destroy helper T cells of the immune system

• HIV is a lentivirus – genus of the retroviridae family – produce multi-organ diseases – characterized by long incubation periods and persistent infection – infect a wide range of prime hosts, as well as some non-primate mammals Courgnaud et al. J. Virol. 75: 857, 2001

Two Types of HIV

HIV-1 vs. HIV-2 • HIV-1 – More virulent – Responsible for worldwide epidemic – Severity of infection varies from person to person • HIV-2 – Primarily found in western Africa – Not transmitted as efficiently – Genome more closely related to SIVmm than HIV-1

Origins of HIV-1 likely descended HIV-2 likely descended from SIVcpz from SIVsm Pan troglodytes Sooty Mangabey

Origins of HIV • Researchers claim that these chimps are the source of HIV-1 – Chimps are only rarely infected with SIVcpz – Actual Reservoir maybe a third unidentified primate species • Definite source remains elusive

Zoonosis: How did it happen? • Human killing and eating of chimpanzees • contact with infected blood • ingestion of uncooked or undercooked meat • Chat - polio vaccine • Hypothesis: HIV is a recombinant construct that occurred when SIV from a contaminated vaccine was administered to humans and arose when human antigens were incorporated into the SIV – Two reports in 2001 discount this theory (Blanco P. et al. and Berry N. et al. )

Zoonosis: When did it happen? • Three earliest know HIV infections • 1959 - serum sample from an adult male living in what is now the Democratic Republic of Congo • 1969 - tissue samples from a teenager who died in St. Louis • 1976 - tissue samples from a Norwegian sailor • January 2000 - study by Dr. Bette Korber estimates first case of HIV infection to be 1930 • Study based on complicated computer model of HIV’s evolution and has a 20 yr error margin

Zoonosis: Where did it happen? • The two primates that carry the SIVs most closely related to HIV are indigenous to western Africa

HIV A Brief History of the modern epidemic

In The Beginning. . . • 1675 - Speculation that HIV was first transmitted from chimpanzees to humans • 1926 -1946 - Scientists believe HIV first spread from monkeys to humans • 1959 - First proven AIDS death • 1978 - Gay men in US and Sweden begin showing signs of what is now known as AIDS

The First Indications • 1981 - CDC notices increase in cases of Kaposi’s sarcoma and Pneumocystis carinii pneumonia

Defining The Problem • 1982 - The term AIDS (acquired immune deficiency syndrome) is used for the 1 st time • 1983 - Institut Pasteur isolates HIV-1 CDC issues warning to blood banks about potential problem • 1984 - Dr. Robert Gallo claims discovery of HIV

The Start of the War • 1985 - FDA approves first HIV antibody diagnostic test - First International Conference on AIDS • 1986 - HIV-2 isolated • 1987 - AZT approved by FDA (1 st anti. HIV drug)

Reality Sets In • 1987 - President Reagan says “AIDS” in public - AIDS memorial quilt started

The War Against HIV/AIDS • 1988 - FDA begins granting preapproval distribution status to HIV/AIDS related drugs • 1989 - First licensed HIV-1 diagnostic kit to directly detect virus (rather than antibodies)

Fighting a Losing Battle? • 1991 - 10 million people worldwide are HIV-positive - Magic Johnson publicly announces he is HIV positive

Increasing The Arsenal • 1992 - FDA starts “accelerated approval” process for HIV/AIDS related drugs • 1995 - Saquinavir (Invirase) is first protease inhibitor approved in US - US admits that Institut Pasteur, not Dr. Gallo, discovered HIV • 1996 - Nevirapine (Viramune) first nonnucleoside reverse transcriptase inhibitor approved in US

Current Status • 1997 - 6, 400, 000 Approximate worldwide death total - 22, 000 HIV-positive people in the world • 1998 -2001 - development and approval of new drugs • 2003 - AIDSVAX developed by Vax. Gen fails in large clinical trial » Trial did show statistically significant prevention in African-Americans and other non-Hispanic minorities

AIDS in the US

Transmission & Prevention • Unprotected sex • Vagina, Penis, Anal, Oral • Shared needles • Drugs, Steroids, Tattoo, Piercing • Mother to child • Birth, Breast Feeding • Blood transfusions • Abstinence • Protection during sex • Condom, Latex barrier • Avoiding risky behavior • Not sharing needles, no promiscuous activity

HIV vs. AIDS • HIV causes AIDS by attacking the immune system’s CD 4 T cells. • Normal CD 4 count is between 500 – 1500 CD 4 T cells per ul of blood, while AIDS CD 4 count is less than 200 CD 4 T cells per ul of blood. • AIDS viral load is about 55, 000 HIV RNA copies per ml of blood. • On average, it takes approximately 10 years to develop AIDS from initial infection. • As a person’s CD 4 count decreases, he/she is more prone to opportunistic infections.

HIV in U. S. • As of January 2001, there were about 850, 000 people living with HIV in the U. S. • Approximately 40, 000 new HIV infections occur in the U. S. every year.

AIDS in U. S. Age Cases % 1 – 19 13, 502 1. 7 20 – 34 312, 889 38. 3 35 – 49 399, 244 48. 9 50 – 65+ 90, 513 11. 1 Race White Black Hispanic AIDS Cases 343, 889 313, 180 149, 752 Asian Native 6, 157 2, 537 • As of January 2002, there were 816, 149 reported cases of AIDS in the United States. • As of January 2002, there were 467, 910 reported deaths due to AIDS in the United States.

HIV/AIDS in Africa

HIV/AIDS in Africa • During 2001, there were 3. 4 million new HIV infections, 2. 3 million AIDS deaths in Africa. • As of January 2002, approximately 28 million people are living with AIDS in Africa. • The life expectancy is 47 years with AIDS and 62 years without AIDS.

HIV/AIDS World Wide • • Approximately 42 million people are living with HIV or AIDS. About 5 million people were infected with HIV during 2002. About 3. 1 million people died of AIDS during 2002. Approximately 21. 8 million people have died of AIDS since the epidemic began.