AIDS (acquired immunodeficiency syndrome) is caused by a group of related retroviruses known as HIV (human immunodeficiency viruses). The full name of AIDS can be explained in this way: acquired means that the condition is caught rather than inherited; immune deficiency means that the virus attacks the immune system so there is greater susceptibility to certain opportunistic infections and cancer; and syndrome means that some fairly typical infections and cancers usually occur in the infected person.
Origin of AIDS
The origin of AIDS has not yet been determined. It has been suggested that HIV originated in Africa and then spread to Europe and the United States. Even today, there are monkeys in Africa infected with immunosuppressive viruses that could have mutated to HIV after humans ate monkey meat.
Most likely, HIV entered the United States on numerous occasions as early as the 1950s. Presently, the first documented case is a 15-year-old male who died in Missouri in 1969 with skin lesions now known to be characteristic of an AIDS-related cancer. Doctors froze some of his tissues because they could not identify the cause of death. Recently, these tissues were examined and found to be infected with HIV. Researchers also want to test the preserved tissue samples of a 49-year-old Haitian who died in New York during 1959 of a type of pneumonia now known to be AIDS related.
British scientists were able to show by examining preserved tissues that a Manchester seaman most probably died in 1959 of AIDS. This may be one of the first cases of AIDS because scientists believe the immunosuppressive monkey virus may have evolved into HIV during the late 1950s.
During the 1960s, it was the custom to list leukemia as the cause of death in immunodeficient patients. Most likely some of these people actually died of AIDS. Since HIV is not extremely infectious, it took several decades for the number of AIDS cases to increase to the point that AIDS became recognizable as a specific and separate disease. The name AIDS was coined in 1982, and HIV was found to be the cause of AIDS in 1983-84.
Since that time much has been learned about HIV, but no effective treatment has yet been found. The number of AIDS cases still continues to increase exponentially. The first 100,000 cases in the United States were reported over an eight-year period, and the second 100,000 occurred in only two years.
Prevalence of AIDS Today
Estimates vary but as many as 20 million people worldwide may now be infected with HIV and there could be as many as 100 million individuals infected by the end of the century. A new infection is believed to occur every 15 seconds, the majority between heterosexuals. HIV infections are not distributed equally throughout the world. Since AIDS arose in Africa, it is not surprising that most infected people live in Africa (66%) but new infections are now occurring at the fastest rate in Southeast Asia and the Indian subcontinent, areas which now account for 16% of all those infected. The explosion of the epidemic in Southeast Asia and India is attributed to a commercial sex industry. A study conducted in northern Thailand estimated that of newly infected military recruits, most have a history of sexual contact with female prostitutes.
In the United States, HIV infections are concentrated in certain cities; New York City, San Francisco, and Los Angeles have about one-third of all AIDS cases. But AIDS is spreading to other U.S. cities and rural areas as well. Similarly, infection occurs more frequently among particular groups; African Americans and Hispanics have a higher proportionate number of cases compared to Caucasians. Even so, it should be remembered that HIV poses a threat to all who inject themselves with drugs intravenously and sexually active adults regardless of ethnicity and sexual orientation.
In the United States, one-quarter of all new infections are now occurring among people younger than 22 years of age and this proportion is growing. It would appear, therefore, that young people are not taking the proper precautions to prevent a spread of the disease. As of 1992, AIDS had become the leading cause of death for U.S. men aged 25-44 years and the fourth leading cause of death among women in this age group. The largest proportion of people with AIDS are homosexual men but the proportions attributed to intravenous drug users and heterosexuals is rising. In 1993 for the first time, homosexual males accounted for fewer than half of those newly diagnosed as having AIDS and women now account for 16% of all newly diagnosed cases of AIDS. The rise in the incidence of AIDS among women of reproductive age is paralleled by a rise in the incidence of AIDS in children younger than thirteen. The chance of an infected mother passing HIV to her unborn child is thought to be about 15-25%. Infection can occur by way of the placenta, at the time or birth, or through breast milk.
The number of persons diagnosed as having AIDS is much smaller
than those that are actually infected with HIV. In the United
States, over 3.5 million are believed to be infected with the
virus but only 550,000 are diagnosed as having AIDS. The U.S.
Center for Disease Control and Prevention (CDC) is now using
a new definition for AIDS that allows more persons to be counted
as having AIDS. The new definition includes persons with severely
impaired immune systems without the necessity of their having
come down with a death-threatening disease. People do not die
from an HIV infection; rather they die from the inability to combat
certain diseases as discussed in the next section.
Symptoms of AIDS
Much has been learned about the structure of HIV and its reproductive cycle (Fig. 1). HIV is a virus and viruses do not reproduce until they are inside a host cell. In order to enter a host cell, HIV attaches to a protein in the plasma membrane called a CD4 receptor. HIV is a retrovirus meaning that its genetic material consists of RNA instead of DNA. Once inside the host cell, HIV uses a special enzyme called reverse transcriptase to make a DNA copy of its genetic material. Now the DNA copy integrates into a host chromosome where it directs the production of more viral RNA. Each strand of viral RNA brings about synthesis of an outer protein coat called a capsid. Assembly of the RNA strands and capsids occurs prior to the viruses budding from the host cell. When the virus buds from the cell, it acquires an envelope that consists primarily of host plasma membrane. Many viruses bud from the host cell before it dies.
The immune system, which consists of white blood cells and certain lymphoid organs, usually protects us from disease. Two ways in which the immune system does this is to produce antibodies, proteins that attack foreign proteins called antigens, and to attack infected cells outright. The primary host for HIV is helper T lymphocytes, the type of white blood cell that stimulates B lymphocytes to produce antibodies and cytotoxic T lymphocytes to attack and kill virus-infected cells. Macrophages, which present antigens to helper T lymphocytes and thereby stimulate them, are also under attack. In addition, the virus enters nervous system glial cells, epithelial cells which line the colon, and special cells in the skin called Langerhan cells.
A person develops symptoms of full-blown AIDS when the number of helper T lymphocytes declines to the point that the immune system is no longer able to do its job of protecting the body from disease. In 1993 the definition of AIDS was broadened to include those persons with a severe depletion of helper T lymphocytes (less than 200 per mm3 of blood) and/or who have an opportunistic infection. An opportunistic infection is one that only has the opportunity to occur because the immune system is severely weakened. Persons with AIDS die from one or more opportunistic diseases and not from the HIV infection itself.
It is possible to recognize at least three stages of an HIV infection.
Asymptomatic Carrier
Usually people do not have any symptoms at all after initial infection with HIV. A few (1-2%) do have mononucleosis-like symptoms that may include fever, chills, aches, swollen lymph nodes, and an itchy rash. These symptoms disappear, however, and there are no other symptoms for quite some time. Although there are no symptoms, the person is highly infectious. Large numbers of infected cells can be found in the blood and high concentrations of infectious virus are present in the plasma. But the HIV blood test is not positive; it tests for the presence of antibodies and not for the presence of HIV itself. This means that HIV can still be transmitted even when the HIV blood test is not yet positive.
Once the immune system produces antibodies, the blood test will be positive; no viruses will be detectable and the number of infected cells in circulation may drop to fewer than one in a million lymphocytes. Until recently it was believed that these circumstances meant that the HIV infection had become latent. But investigators who counted a large increase in the number of helper T lymphocytes after giving an antiviral drug, have reasoned that instead there is a great unseen struggle going on between HIV and helper T lymphocytes. This struggle is ordinarily not seen because the body stays ahead of the hordes of viruses entering the blood by producing as many as one to two billion new helper T lymphocytes each day. As long as the body is able to keep pace with the virus, the number of detected viruses in the blood and the number of infected helper T lymphocytes stays low and the individual stays healthy.
Pre-AIDS
Several months to several years after infection, symptoms most likely will begin to appear. The most common is swollen lymph nodes in the neck, armpits, or groin that persist for three months or more. Other symptoms that indicate pre-AIDS are severe fatigue not related to exercise or drug use; unexplained persistent or recurrent fevers, often with night sweats; persistent cough not associated with smoking, a cold, or the flu; and persistent diarrhea. Also possible are signs of nervous system impairment, including loss of memory, inability to think clearly, loss of judgment, and/or depression.
When the individual develops non-life-threatening but
recurrent infections, it is a signal that full-blown AIDS
will occur shortly. One possible infection is thrush, a fungal
infection that is identified by the presence of white spots and
ulcers on the tongue and inside the mouth. The fungus may also
spread to the vagina, resulting in a chronic infection there.
Another frequent infection is herpes simplex, with painful and
persistent sores on the skin surrounding the anus, the genital
area, and/or the mouth.
Full-Blown AIDS
The majority of people with pre-AIDS eventually develop full-blown AIDS. At this time a blood count of 200 helper T lymphocytes per mm3 is characteristic and the lymph nodes have lost many of their specialized cells so vital to normal immunity. The patient, who is now suffering from "slim disease" (as AIDS is called in Africa)--characterized by severe weight loss and weakness due to persistent diarrhea and coughing--most likely succumbs to one of the opportunistic infections. Some of the opportunistic infections are the following:
Pneumocystis carinii pneumonia. The lungs become useless as they fill with fluid and debris due to an infection with this organism. There is not a single documented case of P. carinii pneumonia in a person with normal immunity.
Mycobacterium tuberculosis. This bacterial infection, usually of the lungs, is seen more often as an infection of lymph nodes and other organs in patients with AIDS. Of special concern, tuberculosis is spreading into the general populace and is multidrug resistant.
Toxoplasmic encephalitis is caused by a one-cell parasite that lives in cats and other animals as well as humans. Many persons harbor a latent infection in the brain or muscle, but in AIDS patients the infection leads to loss of brain cells, seizures, weakness, or decreased sensation on one side of the body.
Kaposi's sarcoma is an unusual cancer of blood vessels, which gives rise to reddish purple, coin-size spots and lesions on the skin.
Invasive cervical cancer. This cancer of the cervix spreads to nearby tissues. This condition has been added to the list because the incidence of AIDS has now increased in women.
Drugs have been developed to deal with opportunistic diseases
in AIDS patients. These drugs help people with AIDS lead a fairly
normal life for some months, but eventually patients are repeatedly
hospitalized due to weight loss, constant fatigue, and multiple
infections. Death usually follows in 2-4 years.
Treatment for AIDS
Most of the drugs available for treatment of AIDS, including the well known drug called AZT, are analogs of nucleotides. Analogs are chemically altered forms so that when reverse transcriptase chooses them instead of a normal nucleotide, reverse transcription stops and viral DNA is not produced. Another class of drugs called proteinase inhibitors, block the action of another viral enzyme called proteinase. Proteinase is required for viral particle maturation at the time of assembly. When HIV proteinase is blocked, the resulting virus lacks the capacity to cause infection. Several proteinase inhibitors are being investigated at this time.
Now that it is apparent that the virus most likely does not have a latent stage, physicians believe that drug therapy should begin as soon as HIV infection has occurred. There is also some basis for believing that therapy with more than one drug at a time may prevent resistance from occurring. Recently, the combination of AZT and 3TC, a new drug analog, seemed to retain the sensitivity of HIV to AZT. Also, there is some hope that the administration of cytokines, such as interleukin-2, might stimulate the immune system to do its job even though clinical trials have not as yet been encouraging in this regard.
Many investigators are working on a vaccine for AIDS. Some are trying to develop a vaccine in the traditional way. Traditionally, vaccines are made by treating a microbe chemically, thereby weakening it so that it can be injected to the body without causing disease. Others are working on subunit vaccines that utilize just a single HIV protein as the vaccine. For example, proteins known as gp120 or gp41 which make up a "spike" that juts from the envelope (see Fig. 1) can be produced by biotechnology and possibly used as a vaccine. More success is expected from the matrix protein p17 because it is not controlled by a gene that mutates like those gp120 and gp41 do. However, the p17 protein is not recognized by macrophages (the cells that present antigens to helper T cells) unless they are attached to a carrier. A liposome, an artificial membranous sac, is one possible carrier. The protein p24 which occurs in the capsid is another candidate for a vaccine.
A novel idea is to administer antibodies against the CD4 receptor. Perhaps these antibodies will attach to CD4 receptors in helper T lymphocytesí plasma membranes, and then HIV would not be able to gain entry.
The various vaccines are at different stages in their development. Thus far, certain vaccines have caused antibodies to appear but none of the vaccines has prevented future infection. Still it may be helpful to use a vaccine in persons who already are infected. After a person has had an HIV infection for some time, mutant forms of the virus arise; most likely full-blown AIDS develops when one mutant gets out of control and takes over. A vaccine that controls just one type of mutant might still be helpful if it allowed the patient's immune system to concentrate on putting other types of mutations out of commission.
Transmission
Figure 2 gives statistics for the distribution of AIDS among adults worldwide and in the United States. By studying the distribution of AIDS we have learned that sexual behaviors and drug-related activities are the major means by which AIDS is transmitted in the United States. Essentially HIV is spread by passing virus-infected T lymphocytes found in semen or in blood from one person to another. Mother's milk that contains infected lymphocytes or a transfusion of infected blood or blood products are other ways in which HIV is spread. Blood and blood products are now tested for the presence of HIV and so the risk of contracting an infection in this manner is now considered very unlikely.
The following behaviors will help prevent the spread of AIDS and decrease the projected number of new cases. At present, there is no other way to stop the AIDS epidemic.
AIDS is primarily a sexually transmitted disease.
Therefore:
1. Abstain from sexual intercourse or develop a long-term monogamous (always the same partner) sexual relationship with a partner who is free of HIV.
2. Refrain from multiple sex partners or having relations with someone who has multiple sex partners. If you have sex with two other people and each of these has sex with two people and so forth, the number of people who are relating is quite large.
3. Remember that the incidence of AIDS is presently higher among homosexuals and bisexuals than among those that are heterosexual (Fig. S3). Also, having relations with an intravenous drug user is risky because the behavior of this group risks AIDS. Also, anyone who already has another sexually transmitted disease is more likely to contract AIDS.
4. Avoid anal-rectal intercourse during which the penis is inserted into the rectum because this behavior increases the risk of infection. The lining of the rectum is thin and infected T lymphocytes can easily enter the body here. Also, the rectum is supplied with many blood vessels and insertion of the penis into rectum is likely to cause tearing and bleeding that facilitate their entrance. The vaginal lining is thick and difficult to penetrate but the lining of the uterus is only one cell thick and does allow infected T lymphocytes to enter. Uncircumcised males are more likely than circumcised males to become infected because vaginal secretions can remain under the foreskin for a long period of time.
5. Practice safe sex. If you do not know for certain that your partner has been free of HIV for the past five years, always use a latex condom during sexual intercourse. Be sure to follow the directions supplied by the manufacturer. Use of a spermicide containing nonoxynol-9 in addition to the condom can offer further protection because nonoxynol-9 also kills the virus and virus-infected lymphocytes.
6. Avoid fellatio (kissing and insertion of the penis into a partner's mouth) and cunnilingus (kissing and insertion of the tongue into the vagina) because they may be a means of transmission. The mouth and gums often have cuts and sores that facilitate the entrance of infected T lymphocytes.
Drug use transmits HIV. Intravenous drug users are the second largest group of persons with AIDS because they tend to share syringes and needles. Intravenous drug use is a way by which an HIV infection spreads to women and then to children.
Therefore:
1. Stop, if necessary, or do not start the habit of injecting drugs into veins.
2. If you are a drug user and cannot stop your behavior, then always use a new sterile needle for injection or one that has been cleaned in bleach.
3. Aside from intravenous drug use, do not use alcohol or any
drugs in a way that may prevent you from being able to control
your behavior.
Although there has been much education about the transmission of AIDS there are still some myths that are unfounded. You cannot get an HIV infection from:
1. inanimate objects such as toilets, doorknobs, telephones, office machines, or household furniture.
2. shaking hands, hugging, social kissing, coughing, or sneezing.
3. everyday contact with people around you in school, in the workplace, at parties, stores, or swimming pool.
4. a mosquito bite. Also, you cannot get an HIV infection from bed bugs, lice, flies, or other insects.
5. eating food prepared by someone with HIV or by using a drinking glass or eating utensil in a public restaurant.
SELECTED KEY TERMS
AIDS (acquired immunodeficiency syndrome) Condition of reduced immunity, after acquiring an HIV infection, now defined by a severe depletion of helper T lymphocytes or by the presence of an opportunistic infection considered characteristic of the disease.
antibody Protein secreted by B lymphocytes in response to an antigen such as a protein in the envelope or capsid of an HIV.
antigen Proteins or glycoproteins that can cause an immune response because they are foreign to the body.
CDC (Centers for Disease Control) Official U.S. government public health bureau responsible for tracking and preventing diseases in the United States.
cytotoxic T lymphocytes The type of T lymphocyte that has the ability to kill a virus-infected cell upon contact.
helper T lymphocyte The type of lymphocyte that stimulates cytotoxic (killer) T lymphocytes to kill virus-containing cells and B lymphocytes to produce antibodies.
HIV (human immunodeficiency viruses) Infection with one or more of these types of viruses usually leads to having AIDS.
immunity Ability of the immune system to resist an infection. The immune system includes white blood cells such as lymphocytes, and macrophages and lymph nodes, among other organs. (See chapter 14).
macrophage A type of white blood cell that engulfs microbes and presents their antigens to helper T lymphocytes so that T lymphocytes are activated.
retrovirus A virus that has RNA as its genetic material and that uses the enzyme reverse transcriptase in order to make a DNA copy of its genetic material.
sexually transmitted disease (STD) any disease that is transmitted through sexual relations.
virus A microbe that consists of genetic material, either DNA or RNA, surrounded by a capsid (protein coat) and an envelope if the virus buds from the host cell. Viruses must reproduce inside a living cell. 000
FURTHER READINGS
Alcamo, I. E. 1993. AIDS: The biological basis. Dubuque, Iowa: Wm. C. Brown Publishers. This easily understood book focuses on the biological basis of AIDS.
Anderson, R. M. and May, R. M. 1992. Understanding the AIDS pandemic. Scientific American 266(5):58. Mathematical models untangle the biology of the AIDS infection in individuals and its transmission in communities.
Aral, S. O., and Holmes, K. K. 1991. Sexually transmitted diseases in the AIDS era. Scientific American 264(2):62. Gonorrhea and syphilis have nearly disappeared, except in the United States.
Bugg, C. E., et al. 1993. Drugs by design. Scientific American 269(6):92. Outlines an innovative approach to developing drugs, which has given rise to many promising new therapeutic agents.
Cohen, P. T., et al. 1994.. The AIDS knowledge base Boston: Little, Brown and Company. A comprehensive text on HIV disease.
Cox, F. D. 1994. The AIDS Booklet. 3rd ed. Madison, Wisconsin: Brown and Benchmark Publishers. A short book that covers essential information.
Fan, H., et al. 1994. The biology of AIDS. 3rd ed. Boston: Jones and Bartlett Publishers. Provides a firm scientific overview of AIDS to the nonspecialized student.
Greene, W. C. 1993. AIDS and the immune system. Scientific American 269(3):98. Although effective treatments and vaccines are still beyond reach, current findings offer some encouragement.
Johnson, H. M., et al.1992. Superantigens in humans. Scientific American. 266(4):92. Investigators are learning how superantigens overstimulate the immune system and induce diseases such as arthritis, toxic shock, and AIDS.
Nowak, M. A. and McMichael, A. J. How HIV defeats the immune system. Scientific American 273(2):58. Full-blown AIDS results when the proliferating virus finally overwhelms the body's defenses, a process that may take years.
Science & Medicine. 1994. 1(1):44. Prospects for an HIV vaccine. Development of an HIV vaccine requires a greater understanding of the infection and the virus.
Scientific American Science & Medicine. Each issue contains the section entitled "AIDS Day by Day" which contains up-to-date AIDS research findings.
Scientific American. 1993. 269(3). Special issue devoted
entirely to the immune system, its function; includes discussions
of AIDS, allergies, and therapeutic agents.