20071011

AIDS

AIDS, or acquired immune deficiency syndrome, is a lethal disease that permanently disables the body's immune system. AIDS is characterized by a variety of debilitating symptoms that leave the body open to attack by one or more specific diseases, such as pneumonia, meningitis, or cancer. In the early years of the 21st century, nearly 40 million people are infected with the virus that causes AIDS, with an additional 20 million having already lost their lives to the disease. Although the number of new cases in highly industrialized nations has leveled off since the 1980s, the number has skyrocketed in Africa, Asia, and Latin America. In the United States, more than 925,000 are afflicted with the AIDS virus, and the disease has caused more than 520,000 deaths.

The disease was first recognized in 1981, when a number of previously healthy homosexual men in Los Angeles and New York City developed Pneumocystis carinii, a rare parasitic disease of the lungs. At the same time, there was also a notable increase in cases of Kaposi's sarcoma, a rare form of cancer previously seen only in elderly men. It soon became apparent that there was a growing epidemic of opportunistic infections, disorders associated with a depressed immune system. Since that time, the virus has gradually progressed: AIDS cases have been reported in almost every country.

The Human Immunodeficiency Virus

The causative agent of AIDS is a retrovirus. Retroviruses contain an enzyme called reverse transcriptase that enables the virus to replicate in a host cell. The AIDS virus was recognized independently by French researchers in 1983 and Americans in 1984. The French named the virus "lymphadenopathy-associated virus" or LAV; the Americans called their discovery the "human T-cell lymphotropic virus type III" (HTLV-III). Then, in 1986, the International Committee for the Taxonomy of Viruses designated "human immunodeficiency virus" (HIV) as the accepted name.

Since HIV was first identified, scientists have learned much about the virus and its mechanisms. However, despite the intensive worldwide biomedical effort against the disease, and the unprecedented speed with which knowledge has been accumulated, many questions remain. A vaccine, considered the best hope of stopping the AIDS epidemic, remains to be developed.

Pathology of AIDS

The immune system is the part of the body that fights infection and disease. It responds differently to various pathogens (disease-causing agents). Those pathogens that induce an immune response are foreign proteins called antigens.

To fight infection the body produces T cells and B cells, which are produced in the lymphatic system and are called lymphocytes. When an antigen is present in the body, T cells process the antigen so that it can then be recognized by B cells. The B cells produce antibodies that match the specific antigen. The antibody binds to the antigen, thus rendering the pathogen susceptible to attack and destruction by the infection-fighting phagocytes. If the body produces antibodies against a specific pathogen once, then memory B cells can produce new antibodies if a subsequent attack by the same pathogen occurs.

HIV acts differently from most pathogen organisms. It is this difference that makes it such a threat. When HIV enters the body, it seeks out T-helper lymphocytes, special cells that help other lymphocytes produce antibodies. Because these cells carry a molecule known as CD-4 on their surfaces, they are also referred to as CD-4 + T cells, or simply CD-4 cells. The CD molecules on these cells happen to serve as ideal receptors for HIV, so the invading virus seeks out CD-4 cells. When HIV locates one, the virus incorporates itself into the cell. Once inside, the HIV either reproduces so quickly that it destroys its host cell, or it replicates slowly, sending out more virus particles to attack other CD-4 cells.

HIV can duplicate itself because of its reverse-transcriptase enzyme. This substance enables the virus' genetic material, ribonucleic acid (RNA), to act as a blueprint for production of deoxyribonucleic acid (DNA). The DNA then transmits the hereditary characteristics to the next generation of HIV.

The destruction of CD-4 cells by HIV leaves the body vulnerable to attack by other pathogens. Although the lymphocytes still produce antibodies to match the HIV antigen, no binding occurs to neutralize the HIV. As a result, the HIV antibodies do not help the body eliminate the HIV.

Once infection occurs, AIDS takes time to develop. Initially, many people with HIV have no symptoms at all. Others develop an acute but transient flulike illness with such symptoms as fever, chills, night sweats, skin rashes, and diarrhea.

People develop full-blown AIDS when their supply of CD-4 cells becomes so depleted that opportunistic infections are able to take advantage of the body's impaired immune system. The more serious of these infections include Kaposi's sarcoma, Pneumocystis carinii, disseminated mycobacteriosis (a bacterial disease), and cryptosporidiosis (a fungus). AIDS can also cause life-threatening weight loss, often called "wasting syndrome," and neurological problems.

As doctors have learned more about how the disease manifests itself, they have expanded the roster of opportunistic illnesses that define cases of full-blown AIDS. Various additions to this list include pulmonary tuberculosis, recurrent pneumonia, and, in women, invasive cancer of the cervix. In addition, doctors use the actual count of CD-4 cells in persons with AIDS as a measure to classify the severity of HIV-related clinical conditions.

The period of time between becoming infected with HIV and developing AIDS varies considerably from person to person. Babies who become infected at birth often get sick before they are a year old. Some infected adults also rapidly develop AIDS, but others remain healthy for a decade or longer. One study found that 18 percent of HIV-infected hemophiliacs may live 25 years before developing full-fledged AIDS.

Findings indicate that, from the time of infection, a continual battle occurs between the viruses and the body's immune system. Each day, as many as 1 billion new viruses are produced, and the body produces up to 1 billion new CD-4 cells to fight them. Losses—on both sides—are equally staggering. Gradually, however, it seems that the body cannot keep up; more and more CD-4 cells are killed than are replaced, and eventually the person becomes vulnerable to opportunistic infections.

Transmission

HIV is transmitted from an infected person to a healthy person in three main ways: sexual intercourse; sharing needles or syringes in the use of intravenous drugs; or from a mother to her child before, during, or shortly after birth.

Most AIDS cases in North America and throughout most of Europe have occurred among intravenous drug abusers, homosexual men, and bisexual men, as well as their sexual partners. In the United States, 11 percent of all adult AIDS cases in 2000 were contracted through heterosexual contact: 5 percent of men and 40 percent of women. Proportionally, in the United States, the spread of HIV through heterosexual contact is growing more rapidly than is its spread via other avenues.

The spread of AIDS leveled off in the United States during the 1990s. However, between 2000 and 2001, the number of diagnosed AIDS cases rose 1 percent, the first increase since 1993. Officials attribute the rise in HIV infections in part to increased risky sexual behavior.

In 1992, women accounted for 13.8 percent of persons living with AIDS; in 2001, the proportion exceeded 23 percent. Although African-Americans constitute only 12 percent of the population, they accounted for half of the new HIV infections reported in 2001.

In Africa and Asia, the primary route of transmission is via heterosexual contact. In response, the United Nations program on AIDS instituted a Global Strategy Framework on HIV/AIDS, with a particular focus on educating youth.

Some people who received transfusions of contaminated blood in the early 1980s were also infected with HIV and have since developed AIDS—and in many cases, died from the disease. Since 1985, when a test to determine the presence of HIV first became available, the blood supply in the United States and many other nations has been screened for HIV. Individuals who donate blood products are also screened.

No evidence supports the possibility of transmission by casual social contact. Nor have researchers observed any household transmission among family members and friends of persons with AIDS through close, but nonsexual, contact. Likewise, the virus has not been observed to spread via water, air, food, contact with inanimate objects, contact with raw sewage, or via insects such as mosquitoes. Although many bacteria and viruses are spread by these routes, HIV is not one of them. HIV has been found in the saliva and tears of infected persons, but these fluids have not been found to transmit the virus. In fact, these fluids contain HIV-killing proteins called lysozymes.

Testing for AIDS

In 1984 a test called the enzyme-linked immunosorbent assay (ELISA) was developed that can determine whether an individual is carrying HIV. The test does not detect the virus itself. Rather, it detects antibodies to HIV. If a tested person is found to be infected, or "positive," the test is often confirmed by another procedure known as a Western blot. Scientists now make use of a technique known as the polymerase chain reaction (PCR). This procedure, developed for use in the field of molecular biology, makes it possible to amplify tiny quantities of DNA. Scientists have used PCR to amplify quantities of viral DNA from the blood of HIV-infected persons. This has helped them to learn more about how the virus works.

Most people develop antibodies within 12 weeks of infection. If a person is tested after becoming infected but before developing antibodies, the results will be "negative"—yet the individual is carrying the virus and is capable of infecting others. There is also evidence that people are extremely contagious in the first eight weeks after getting HIV—a period during which they cannot know that they are infected.

Treatment

There is no known cure for AIDS. And until 1995 there was no evidence to suggest that anyone who had become infected with HIV had been able to regain a normally functioning immune system. In 1995, it was reported that a 5-year-old boy infected at birth appeared to have fought off the virus by age 1; after that time, his body reportedly remained free of the virus.

Research facilities around the world design and test hundreds of possible treatments for AIDS. As more has been learned about the basic biology of the disease, there have been changes in the focus of research efforts and also changes in how and when people receive treatment. For example, it has been found that most cases of pediatric AIDS can be prevented if infected women take the drug AZT (azidothymidine) while they are pregnant.

AZT, the first drug licensed by the U.S. Food and Drug Administration (FDA) for AIDS treatment, is an antiviral agent. It inhibits HIV's reverse transcriptase enzyme, thus slowing reproduction and allowing the population of CD-4 cells to rebound, at least temporarily. AZT has usually been used with other drugs, such as DDI (didanosine), nevirapine, and indinavir. The grouping of such drugs has been nicknamed the "AIDS cocktail." By early in the 21st century, more than 25 drugs were being used in the treatment of HIV infection. In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), which interrupt the early stage of the virus and include AZT, they are classified as nonnucleoside reverse transcriptase inhibitors (NNRTIs), which include nevirapine; protease inhibitors, which interrupt virus replication at a later stage of its life cycle; and fusion inhibitors. Since HIV can become resistant to any drug, a combination treatment may be used to suppress the virus. When NRTIs and protease inhibitors are given in combination, it is called highly active antiretroviral therapy (HAART). Such treatment can be available both to people newly infected with HIV as well as to AIDS patients. HAART has not only reduced the number of deaths from AIDS, but it also has improved the health of those afflicted with the disease. It is not a cure, however, and severe side effects can result. Patients receiving the therapy must be monitored closely.

Another promising avenue of treatment being investigated is the use of interleukin 2, a natural protein that regulates the body's immune defenses. Early studies indicate that infusions of this drug help increase CD-4 counts in people who are HIV-positive but have not yet developed AIDS.

Improvements also have been made in fighting the infections that threaten AIDS patients. For example, an aerosol drug known as pentamidine has been effective in treating the life-threatening illness Pneumocystis carinii pneumonia (PCP), which sometimes occurs repeatedly in AIDS patients. Drugs such as trimethoprim, sulfa, and atovaquone have also been effective.

Despite the promise of these various therapeutic approaches, there is widespread agreement among those in the medical community that achieving a "cure" for AIDS is not likely in the near future. A more obtainable objective is to control HIV and opportunistic infections, thus allowing people to remain relatively healthy for as long a period of time as possible.

Vaccine Research

A major quest of AIDS research is the development of a vaccine that will prevent HIV infection. In order to be successful, a vaccine must, in effect, "fool" the body's immune system into responding to what is actually a harmless threat, so that when the real viral enemy comes along, the body will already know how to fight it.

Scientists are continuing to experiment with various immunogens—substances that will evoke an immune response that protects against HIV. Some of the immunogens being evaluated include weakened or inactivated forms of the virus itself, or certain of its protein subunits. Another potential approach is the use of gene therapy. This would make CD-4 cells resistant to HIV infection by introducing an HIV-resistance gene directly into the cells.

Most vaccines are in Phase I trials, which assess safety. Several are in Phase II, dosage evaluation. In 2003, Phase III trials were completed on two vaccines—VaxGen's AIDSVAX B/B and AIDSVAX B/E—which proved to be ineffective. Meanwhile, efforts to produce an AIDS vaccine continue. The AIDS Vaccine Advocacy Coalition (AVAC) calls the ongoing development project "a long-term mission," maintaining that a vaccine would not be ready by 2007, a goal that had originally been set by President Bill Clinton and his administration.

Future Outlook

Clearly, the most profound impact of the AIDS epidemic is yet to come. The number of HIV infections and cases of AIDS continues to grow, creating prospects of a grim future, particularly in Africa and Asia. Providing health care for patients will require billions of dollars. In the United States, the cost of caring for a person with AIDS ranges from $14,000 to more than $34,000 per year. A substantial part of these costs is the price of drugs. Such high costs are even a greater problem in the poorer nations where AIDS has become so rampant. In response, the 2001 United Nations conference on AIDS called for $9 billion for a global AIDS fund. In 2003, U.S. President George W. Bush announced a new program to fight AIDS in Africa, pledging $15 billion to the cause.

It is critical that education about HIV and AIDS be promoted on a global scale, so that people make behavioral changes that will limit further transmission of the virus.

There are some bright spots on the horizon. Each year, scientists have a better understanding of how HIV works, and how the human immune system reacts to the virus. New drugs offer improved treatment. By the early 2000s, people infected with HIV were living longer than were patients in the early stages of the epidemic. There is hope that ever-more-sophisticated strategies will allow infected individuals to live longer before symptoms occur, and that some people with HIV may never develop AIDS.

The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies.

Copyright Information: Public domain information with acknowledgement given to the U.S. National Library of Medicine.

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