Acquired immunodeficiency syndrome (AIDS) is caused by a group of related retroviruses known as HIV (human immunodeficiency viruses). In the United States, AIDS is usually caused by HIV-1, which enters a host by attaching itself to a plasma protein called a CD4 receptor. HIV-1 infects helper T cells, the type of lymphocyte that stimulates B cells to produce antibodies and cytotoxic T cells to destroy virus-infected cells. Macrophages, which present antigens to helper T cells and thereby stimulate them, are also under attack. 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 (called cDNA) of its genetic material. Now cDNA 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. The viral enzyme protease is necessary to the formation of capsids. Capsids assemble with RNA strands to form viruses, which bud from the host cell.
Transmission of AIDS
HIV infection spreads when infected cells in body secretions, such as semen, and in blood are passed to another individual. To date, as many as 64 million people worldwide may have contracted HIV, and almost 22 million have died. A new infection is believed to occur every 15 seconds, the majority in heterosexuals.
HIV infections are not distributed equally throughout the world. Most infected people live in Africa (66%) where the infection first began, but new infections are now occurring at the fastest rate in Southeast Asia and the Indian subcontinent.
HIV is transmitted by sexual contact with an infected person, including vaginal or rectal intercourse and oral/genital contact. Also, needle-sharing among intravenous drug users is high-risk behavior. Babies born to HIV-infected women may become infected before or during birth, or through breast-feeding after birth.
HIV first spread through the homosexual community, and male-to-male sexual contact still accounts for the largest percentage of new AIDS cases in the United States. But the largest increases in HIV infections are occurring through heterosexual contact or by intravenous drug use. Now, women account for 20% 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 13.
Phases of an HIV Infection
The Centers for Disease Control and Prevention recognize three stages of an HIV-1 infection, called categories A, B, and C. During the category A stage, the helper T-lymphocyte count is 500 per mm3 or greater (Fig. 13A). For a period of time after the initial infection with HIV, people don’t usually have any symptoms at all. 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 no other symptoms appear for quite some time. Although there are no symptoms, the person is highly infectious. Despite the presence of a large number of viruses in the plasma, the HIV blood test is not yet positive because it tests for the presence of antibodies and not for the presence of HIV itself. This means that HIV can still be transmitted before the HIV blood test is positive. Several months to several years after a nontreated infection, the individual will probably progress to category B, in which the helper T-lymphocyte count is 200 to 499 per mm3. During this stage, the patient may experience swollen lymph nodes in the neck, armpits, or groin that persist for three months or more. Other symptoms that indicate category B 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. The development of non-life-threatening but recurrent infections is a signal that the disease is progressing. 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. Previously, the majority of infected persons proceeded to category C, in which the helper T-lymphocyte count is below 200 per mm3 and the lymph nodes degenerate. The patient is now suffering from AIDS, characterized by severe weight loss and weakness due to persistent diarrhea and coughing, and will most likely contract 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, such as Pneumocystis carinii pneumonia, Mycobacterium tuberculosis, toxoplasmic encephalitis, Kaposi’s sarcoma, or invasive cervical cancer. This last condition has been added to the list because the incidence of AIDS has now increased in women.
Figure 13A Stages of an HIV infection. In category A individuals, the number of HIV in plasma rises upon infection and then falls. The number of CD4 T lymphocytes falls, but stays above 400 per mm3. In category B individuals, the number of HIV in plasma is slowly rising, and the number of T lymphocytes is decreasing. In category C individuals, the number of HIV in plasma rises dramatically as the number of T lymphocytes falls below 200 per mm3.
Treatment for AIDS
Therapy usually consists of combining two drugs that inhibit reverse transcriptase with another that inhibits protease, an enzyme needed for formation of a viral capsid. This multidrug therapy, when taken according to the manner prescribed, usually seems to prevent mutation of the virus to a resistant strain. The sooner drug therapy begins after infection, the better the chances that the immune system will not be destroyed by HIV. Also, medication must be continued indefinitely. Unfortunately, an HIV strain resistant to all known drugs has been reported, and persons who become infected with this strain have no drug therapy available to them. The likelihood of transmission from mother to child at birth can be lessened if the mother takes an inhibitor of reverse transcriptase called AZT and if the child is delivered by cesarean section. Many investigators are working on a vaccine for AIDS. Some are trying to develop a vaccine in the traditional way. Others are working on subunit vaccines that utilize just a single HIV protein as the vaccine. So far, no method has resulted in sufficient antibodies to keep an infection at bay. After many clinical trials, none too successful, most investigators now agree that a combination of various vaccines may be the best strategy to bring about a response in both B lymphocytes and cytotoxic T cells.