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.