AIDS AT 20 WILL WE FIND A CURED?

If you don't hear about it for a while, it's easy to forget that AIDS continues to be one of the world's stealthiest killers. It's been 20 years since mystified doctors recorded the cases of five men in Los Angeles who died from a rare pneumonia, or lung infection. Those cases turned out to be a startling new disease--AIDS, or acquired immune deficiency syndrome. Today, the disease is the fourth-leading cause of death worldwide and number one in Africa--where AIDS has massacred 17 million people and left 12 million orphaned, whose parents were AIDS casualties. In the first two decades, the death toll from the pandemic (widespread disease) has soared to a mind-boggling 22 million globally, including 450,000 Americans. "Until AIDS, most of us thought of catastrophic plagues, like the Black Death and Spanish-flu epidemic of 1918, as things of the past," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Last year alone, 5.3 million people around the world--15,000 a day!--became newly infected with HIV, or human immunodeficiency virus. HIV is the virus, a disease-causing microscopic particle, that eventually triggers full-blown AIDS. Nearly 1 million Americans are now HIV-infected, according to the U.S. Centers for Disease Control. Around one third of these people have no clue they're infected. Others, like Stephanie Zepeda, 15, of Stockton, California, know it only too well: "I was born with HIV," she says. Her biological parents died of the disease; she learned she was infected when her adoptive mother told Stephanie at age 9.

STILL INCURABLE

In the last two decades, scientists have developed a battery of drugs that have turned AIDS from a certain death sentence into a more manageable, if chronic, condition. AZT, an antiviral drug that tries to block HIV before it reproduces in cells, was introduced in 1987; a decade later, a class of drugs called protease inhibitors, which attack the virus as it forms inside cells, hit the market. But these drugs can only slow, not stop, the pace of HIV. And their cost--easily $15,000 a year--lies far beyond the reach of most patients, especially those in underdeveloped countries.

Last June, the United Nations General Assembly convened its first special session ever to address a disease--AIDS. The result: all 189 member nations signed a historic "Declaration of Commitment" to reduce HIV infection rates by 25 percent in the most besieged countries by 2005. The effort will require increased global funding for treatment and further research. For after 20 years, AIDS remains unstoppable and incurable.

Who
has
AIDS?

PERCENTAGE
OF PEOPLE
(15-49 years old)

LIVING WITH
HIV/AIDS, 1999(*)

AIDS/HIV rate
in the U.S.:
0.61%

Highest
rate in Latin
America:
Guyana, at 3%

Highest rate in
Western Europe:
Portugal, at 0.74%

Highest rate
in Asia:
Cambodia,
at 4%

(A) = 15%-36%
(B) = 5%-15%
(C) = 1%-5%
(D) = 0.5%-1%
(E) = 0.1%-0.5%
(F) = 0%-0.1%
(G) = No data

Now scientists are pinning their best hopes for prevention on a vaccine--a benign form of a virus injected into the body to trigger antibodies, protein particles that kill disease-causing germs. But since 1987, more than 50 experimental HIV vaccines have been tested on people; so far, none has worked. Why? Like other viruses, HIV targets and destroys a specific body cell. But in this case, the cell happens to be a key player in the immune system, the very network of organs and cells that protects the body against infection. "Unless we find a definitive vaccine, which is questionable, we may not see an end to the pandemic in our lifetime," says Margaret McCluskey, a vaccine-study coordinator in Washington, D.C.

A KILLER'S PATH

In the last two decades, no previously known virus has ever been studied as thoroughly as HIV. And learning to understand the virus has blown open the window for scientists to decipher how the intricate human immune system works (see "The Immune System The Ultimate Defender"). In the pandemic's early years, endless myths and fears abounded about how one contracted HIV--from kissing, toilet seats, or mosquito bites, for example. By the mid-80s, however, epidemiologists (scientists who study diseases) concluded HIV is transmitted from person to person only by the direct exchange of body fluids or blood--through unprotected sexual contact, sharing of intravenous needles or infected blood transfusions, or from mother to unborn child.

The Immune System The Ultimate Defender

The immune system is a complex network of organs and cells that defend the body from infection.

Lymph nodes The fluid called lymph helps remove bacteria from body tissues. Lymph nodes filter out bacteria from lymph, then return lymph into circulation.

Bone marrow All immune cells are initially produced here, including 16 general types of white blood cells--each with a different job.

Thymus This gland-like structure produces mature T-cells.

Spleen The pulpy organ serves as an "immune filter" for blood. It captures foreign materials--or antigens.

T-CELL ATTACK

Killer T-cells attack cells infected by viruses. They multiply and liquidate infected cells with toxic chemicals. One small group of T-cells, called "memory cells," remember a virus in case it strikes again.

While other viruses like measles and chicken pox are airborne and spread by casual contact, HIV is so fragile outside the body it quickly dies when exposed to air, water, or heat. Once inside the body, however, the virus proves nearly indestructible. Over the years, researchers have slowly pieced together HIV's lethal course:

* Each HIV particle consists of merely 9 genes (chemical instructions), encased in a protein shell; scientists have decoded all 9 genes. When the virus enters the body, it ravenously attacks an immune-system cell--a white blood cell called a helper T-cell (see "The Life Cycle of HIV").

The Life Cycle of HIV

In 20 years, scientists have learned much about HIV's life cycle: 1. Knob-shape proteins on the HIV surface bind to receptors on a healthy T-cell. The virus invades the cell. 2. HIV is a retrovirus--it converts RNA into DNA (both genetic material) to reproduce. 3. New viral DNA splices itself into a T-cell's own DNA. 4.-6. In a complex process, HIV reproduces itself in the T-cell. It releases RNA copies, which combine with viral proteins. 7.-8. New HIV particles bud from T-cells that have been turned into virus factories. Other immune cells now try to destroy infected T-cells.

* Ordinarily, this T-cell acts as a kind of immune-system "general": It activates the production of both antibodies and "foot soldiers" (called killer T-cells), which poison virus-infected cells in the body. But in this case, HIV overtakes a helper T-cell's machinery, turning it into a factory that can churn out one hundred million HIV copies in a drop of blood. So eventually the killer T-cells attack the helper T-cells--their own generals.

Doctors think most infected people develop often-severe flu-like symptoms during this critical period, when they may not know they're infected. But the symptoms soon disappear. (An antibody blood test indicates HIV infection after 8 to 12 weeks.)

* The immune system mounts its initial assault against HIV. The generals (helper T-cells) launch a two-sided strategy: First, in a process called antibody-mediated immunity, millions of antibodies stick to HIV particles and block them from attacking cells. Second, in what's called cell-mediated immunity, killer T-cells shower HIV-infected cells with poisons.

* Imagine a silent battlefield in the body: at one time HIV has the upper hand, at another, the immune system. The battle can go on for years, even while the patient feels symptom-free. But gradually more and more helper T-cells are destroyed. "It's as though you have this infantry, but no generals telling them what to do," says Dr. Bruce Walker, an infectious-disease specialist at Massachusetts General Hospital in Boston. Over time, the immune system becomes permanently depleted.

* Ultimately HIV wins. Two crucial factors: Even with drugs that reduce the virus to undetectable bloodstream levels, it hides in body tissue for life, even in the helper T-cells that battle HIV. "The virus inserts its genes among the cells' own genes, lurking invisibly," says Johns Hopkins University researcher Robert Siliciano. That in itself isn't unusual; the chicken pox virus, for example, permanently hides in nerve cells for life while the immune system usually holds it in check. But since HIV wages war against the immune system, its attack is continual.

Second, HIV continually mutates, or creates new strains, that outwit even the strongest medications. The body finally falls prey to "opportunistic infections" like pneumonia and brain-attacking viruses, which take advantage of the crippled immune system and kill the patient.

VACCINE SEARCH

Over the last decade in North America and Europe, the number of people to become HIV-infected each year has not actually increased. Potent AIDS drugs have slashed annual death rates in developed countries. So why are researchers scrambling to produce an effective AIDS vaccine?

Most of the world's 36 million HIV-infected people can't begin to afford costly medications. Education programs that promote HIV-prevention measures--such as sexual abstinence and not sharing IV needles--often fall on deaf ears. "Prevention campaigns haven't fully worked on a global scale, and I'm not sure they ever will," says Dr. Seth Berkley, head of the International AIDS Vaccine Initiative. "That's why you come back to the need for a vaccine."

Given the endless complexity of HIV, the prospect of a vaccine that totally prevents HIV infection may be impossible. Perhaps the best hope in the next decade is a partial vaccine that helps control infection in an HIV-infected person, or lessens the risk of a healthy person's becoming infected. Some possible vaccines that have been or will be tested on humans:

* Harmless versions of proteins found on HIV's surface shell would be injected. These proteins would stimulate a healthy body to produce enough antibodies to lessen the chance of HIV penetrating T-cells.

* Harmless forms of HIV genes might be injected into a healthy person's body and trigger enough antibodies or more killer T-cells to thwart infection.

* Genetically engineered viruses or bacteria--designed in laboratories--might generate HIV proteins, which when injected into a healthy person would trigger an immune response able to resist an HIV attack.

Years of experimentation lie ahead. It may be another decade before any vaccine is available. After 20 years of AIDS, one fact has remained constant: Prevention is the only cure.

RELATED ARTICLE: AIDS Milestones

In 1981, researchers become aware of a mysterious disease. They search for patterns to discover how it's spread--and who's at risk.

1981

First five AIDS cases reported. Researchers soon learn that AIDS is sexually transmitted and spread by the exchange of infected blood.

1984

The first antibody test to detect HIV is approved.

Scientists at the U.S. National Cancer Institute and Pasteur Institute in France isolate HIV in the lab.

1986

Ryan White makes headlines when barred from school after contracting HIV through a blood transfusion. A hemophiliac (prone to severe bleeding), he dies in 1990.

1987

AZT, the first anti-HIV drug, is approved for experimental use, followed by a host of other drugs.

1991

Basketball great Magic Johnson announces he is HIV-infected. Celebrities use their status to raise funds for AIDS research.

1996

Begun in 1987, the AIDS Memorial Quilt grows to more than 43,000 panels. Its last display in 1996 covers Washington, D.C.'s entire National Mall.

2000

Dr. Seth Berkley heads the International AIDS Vaccine Initiative. He thinks a vaccine is the best approach to halting the global spread of HIV.

Cross-Curricular Connection

[ILLUSTRATION OMITTED]

Culture: Research several myths about AIDS and how it's contracted. Why do the myths spread?

Did You Know?

* New HIV infections in the U.S. peaked at more than 150,000 people per year in the mid-1980s. Since the early 90s, new infections have remained around 40,000 per year. However, infection rates in some American cities are again rising among gay men--one urban U.S. study reveals an HIV-infection rate of 7.2 percent in this group.

* No one dies from AIDS or HIV specifically. Instead, a person with AIDS dies from infections as a result of a disabled immune system. Various cancers--even the common cold--can kill someone with AIDS.

National Science Education Standards

Grades 5-8: structure and function in living systems * personal health * risks and benefits

Grades 9-12: the cell * personal and community health * natural and human-induced hazards

Resources

"AIDS at 20: Special Report," Newsweek, June 11, 2001 Johns Hopkins AIDS Service Life Cycle of HIV Infection animation: www.hopkins.aids.edu/ hiv_lifecycle/hivcycle_txt.html

"On Research Frontier, Basic Questions," by Gina Kolata, The New York Times, June 5, 2001

Frequently Asked Questions on HIV/AIDS: www.cdc.gov/hiv/pubs/faqs.htm