There have been so many cases of AIDS in recent years that few of us have failed to think about the dangers it poses to ourselves or to someone we know. In 1995, the Centers for Disease Control in Atlanta, which keeps track of infectious disease around the country, reported the 500,000th case of full-blown AIDS since 1981, the year the disease was first recognized. According to World Health Organization estimates, by the year 2000 some 40 million people worldwide may be infected with HIV (the virus that causes AIDS), and those who are infected but show no symptoms will continue to infect others. In light of what you now know about the strategies that enable our bodies to resist illness, it is appropriate to review current information about this plague of the twentieth century.

AIDS, acquired immune deficiency syndrome, is caused by a retrovirus identified as human immunodeficiency virus (HIV). A retrovirus is one of a group of RNA viruses that use an infected cell's DNA to reproduce, destroying the host cell's functioning in the process. For many years, retroviruses have been know to cause concern in humans and animals. HIV is one of the first infectious retroviruses to be discovered. Once inside the body, it attacks and destroys the helper T lymphocytes, thereby severely impairing the individuals ability to combat infection. AIDS victims die from a host of opportunistic infections that would pose little threat to individuals with healthy immune systems.

HIV is transmitted through infected blood, semen, or vaginal secretions. A person infected with HIV may be asymptomatic or develop a brief flulike infection, including symptoms of fever, fatigue, headache, and swollen lymph nodes. These symptoms disappear rapidly, however, so that the person is unaware that he or she has contracted a deadly disease and is potentially dangerous to others.

From 2 weeks to a year or longer after the initial infection, the person's immune system reacts to HIV by producing antibodies that are detectable by blood tests. Antibody levels arise initially, but then fall as the immune system gradually begins to falter. For most people, the first sign that they are infected with the virus is the development of chronically enlarged lymph nodes, usually at several sites in the body. Severe fatigue and fever are other common symptoms.

As the helper T cell population continues to decline, the person moves on to the next level of HIV infection call AIDS-related complex (ARC). The most likely and dramatic visible expression is an extreme weight loss. Contributing to the weight loss is diarrhea, accompanied by a chronic low-grade fever, general fatigue, and a lack of energy. Hairy leukoplakia (white lesions in the mouth), thrush (mouth infection with candida), and night sweats are other symptoms associated with ARC. At this point, the helper T cells are declining rapidly and losing both their ability to secrete lymphokines and to activate some of the nonspecific defense mechanism.

As the disease evolves into full-blown AIDS, the helper T cells are severely weakened and eventually completely destroyed, keeping them from stimulating production of killer T cells and B cells. Without the killer T cells, the system is vulnerable to other viral infections; without the B cells, the system cannot make memory cells or synthesize crucial antibodies. With no ability to synthesize specific antibodies, the entire immune system slips into total chaos. Symptoms at this stage are the same symptoms seen in ARC but intensified; added to them is chronic cough, spots on the skin of the legs, fuzzy speech and in the late stages, dementia.

Once the virus steps up its cellular attacks, the victim is extremely vulnerable to any infection that takes advantage of dysfunctional immune mechanisms. Such pathogens are called opportunistic. (The secondary infections that attack the weakened immune system are what first alerted the medical community to the presence of AIDS. When exotic diseases that were unusual in the general population became more prevalent, immunologists sought explanations.) Opportunistic infections include a previously rare form of cancer known as Kaposi's sarcoma, evidenced by coin-sized purple lesions of the skin. For about 60% of the AIDS patients, pneumocystis carnii pneumonia (PNP) is the opportunistic infection that marks the progression of HIV infection to full-blown AIDS.

Although no cure for AIDS is currently known, treatment is available for many of the infections and cancers that afflict AIDS patients. The drug AZT (zidovudine--formerly called azidothymidine) blocks the action of reverse transcriptase, the enzyme needed by HIV to be incorporated in the host cell's DNA. Recent evidence suggests that AZT is effective in people with full-blown AIDS and may prolong the onset of AIDS symptoms. Additionally, AZT was shown to cut transmission of HIV from mothers to babies by about two-thirds in a study conducted in 1994. Unfortunately, HIV has developed strains that are resistant to AZT; moreover, AZT is costly and has severe side effects. Two other drugs--ddI (dideoxyinosine) and ddC (dideoxycytidine)--also inhibit viral replication and appear to have fewer side effects than AZT. Like AZT, however, they are effective in a patient only for a limited time.

Another class of drugs--protease blockers--inhibit other enzymes (proteases) that HIV needs in order to replicate. A combination of a protease inhibitor with two reverse transcriptase inhibitors has recently been demonstrated to be highly effective at inhibiting viral replication. If the viruses cannot replicate, the immune system might stand a chance to reduce or eliminate the HIV infection. Though exciting, this new drug regimen has severe side effects, is difficult to maintain, and is very expensive.

Many scientists believe that the development of a vaccine is the only way to bring AIDS under control. Most of the vaccines currently in use are made from live viruses that have been sufficiently weakened so that they no longer cause the disease yet stimulate the people who are vaccinated into producing their own antibodies. But with a virus as dangerous as the one that causes AIDS, using a live virus that has been weakened in the conventional way is like playing with a biological time bomb; it is possible that it could somehow regain strength and activate itself.

Advances in recombinant DNA technology have provided AIDS researchers with a new approach--the preparation of a subunit vaccine. Subunit vaccines present no danger of infection because they do not contain any genetic material from the virus; their content is limited to one or more viral proteins or pieces of proteins. To prepare such a vaccine, an attempt is made to identify the viral protein (antigen) most likely to cause a protective antibody response from the human immune system. This protein is usually part of the viral envelope--its outer coat. A hepatitis B vaccine based on this strategy was licensed in 1987. In addition, a subunit vaccine against feline leukemia virus is currently available for immunization of cats. Various subunit vaccines, utilizing different viral proteins, are currently under trial for use against AIDS.

Although progress is being made in the development of a vaccine, it has been hampered by the mutability of HIV. Investigations monitoring the evolution of HIV found as many as 150 different forms of the virus in one individual. Further compounding the problem are the logistics and expense of clinical trials and associated liability issues. For these reasons, mass immunizations against HIV should not be regarded as a reasonable option, at least for the near future.

At present, the only effective prevention of AIDS is to stop the transmission of HIV. Individuals can protect themselves by practicing sexual abstinence before marriage, by practicing safe sex, and by avoiding multiple sex partners. Transmission through contaminated needles could be avoided if intravenous drug users were to use sterile needles only. Blood has been routinely screened for the presence of HIV since 1985. Although infection from donated blood is extremely rare, individuals who will need blood for upcoming operations are encouraged to donate blood ahead of time. Finally, any woman infected with HIV should avoid pregnancy. The normal immune system changes that occur in pregnancy may accelerate severe AIDS problems for a woman who has the virus, and the infection very likely will be transmitted to the baby.

If HIV infection trends persist, the threat of AIDS surely will be a rite of passage for many generations to come. As the search for a vaccine and more effective treatments continues, the best defense available to us is a stepped-up program of public education on how to protect ourselves.

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