human immunodeficiency virus kyle kuhn, gerard jenkins and agnes kazior march 11, 2003

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 HIVHIV-1 likely descended

from SIVcpz

HIV-2 likely descended from SIVsm

Pan troglodytes 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 20yr 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 1st 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 (1st 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 pre-approval 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 non- nucleoside reverse transcriptase inhibitor approved in US

Current Status

• 1997 - 6,400,000 Approximate worldwide death total

- 22,000,000 HIV-positive people in the world

• 1998-2001 - development and approval of new drugs

• 2003 - AIDSVAX developed by VaxGen fails in large clinical trial

» Trial did show statistically significant prevention in African-Americans and other non-Hispanic minorities

AIDS in the US

0

10000

20000

30000

40000

50000

60000

70000

80000

1981 1985 1989 1993 1997 2001

AIDS cases AIDS related deaths

00002-E-4 – 1 Decem ber 2001

Adults and children estimated to be livingAdults and children estimated to be livingwith HIV/AIDS as of end 2001with HIV/AIDS as of end 2001

Western Europe560 000560 000

North Africa & Middle East

440 000440 000Sub-Saharan

Africa28.1 million28.1 million

Eastern Europe& Central Asia

1 million1 million

South& South-East Asia

6.1 million6.1 million

Australia& New Zealand

15 00015 000

North America940 000940 000

Caribbean

420 000420 000

Latin America1.4 million1.4 million

Total: 40 million

East Asia & Pacific

1 million1 million

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 CD4 T cells.• Normal CD4 count is between 500 – 1500

CD4 T cells per ul of blood, while AIDS CD4 count is less than 200 CD4 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 CD4 count decreases, he/she is more prone to opportunistic infections.

HIV in U.S.

HIV by Risk

MSM, 42%

IDU, 25%

HET, 33%

HIV by Race

0% 20% 40% 60%

White

Black

Hispanic

Other

• 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.

• 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.

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 AIDS Cases

White 343,889

Black 313,180

Hispanic 149,752

Asian 6,157

Native 2,537

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.