| Progression of HIV Infection |
Characteristically, an HIV infection can progress for eight to ten years before the clinical syndrome (AIDS) occurs. The long latent period of the virus has contributed to many of the problems relating to diagnosis and control. The basketball player Magic Johnson was still relatively healthy twelve years after he announced he had HIV. On the other hand, not all cases exhibit the long latent period, and abrupt progression to AIDS occurs. Many factors, including genetics, determine the speed at which the disease will progress in a given individual.
The Centers for Disease Control and Prevention (CDC) has identified the stages of a typical HIV infection: Categories A, B, and C. In the first stage, Category A, it can be difficult to determine whether an individual is infected without performing a blood test. While at least half of infected individuals will develop a mononucleosis-like illness (headache, muscle ache, sore throat, fever, and swollen lymph nodes) within three weeks of exposure, some Category A individuals are asymptomatic. Moreover, the symptoms themselves can be the result of many different infections. The presence of a rash may help differentiate an HIV infection from other infections, but not all HIV-infected individuals get a rash. Most of these signs and symptoms subside, but swollen lymph glands and malaise can persist for years through Category A HIV.
The number of virus particles circulating in the bloodstream is usually highest soon after exposure. At this point the CD4 cell population plunges (helper T cells are among the immune cells that express the CD4 receptor, which can be used as a marker for counting cell types). As antibodies to HIV appear the numbers of CD4 cells rise; however, CD4 cell levels drop again as the infection progresses. This lowering of CD4 cell levels typically happens slowly, over the course of years. Category C HIV (clinical AIDS) occurs once CD4 numbers have fallen substantially (to 200/mm3 from the normal level of 800-1200 cells/ mm3).
In the Category B stage indications of immune system failure begin. Persistent infections - such as yeast infections, shingles, diarrhea, and certain cancerous conditions of the cervix - are apparent.
Category C is synonymous with AIDS. In this stage the opportunistic infections associated with AIDS appear. According to the CDC, twenty-six known clinical conditions affect people with AIDS; most are infections that do not usually affect healthy individuals. These include yeast infections of the esophagus, bronchi, and lungs; Pneumocystis pneumonia (a fungal infection); toxoplasmosis (caused by a protozoan that is spread by cats); Kaposi's sarcoma (a rare cancer of the skin caused by a virus); cytomegalovirus (CMV) infections; and tuberculosis. In addition, individuals who have been affected by HIV are more likely to become seriously ill or die than other members of the population during outbreaks of infections such as cryptosporidium (a water-borne parasite) and coccidiomycosis (a dust-borne fungus).
Cytomegalovirus (CMV) causes another opportunistic infection prevalent in AIDS patients. About eighty percent of people in the U.S. have antibodies to this virus, but infections in normal individuals often go undetected or seem like a mild case of mononucleosis. In the immunocompromised, however, CMV can cause life-threatening pneumonia or encephalitis. In AIDS patients CMV that has been latent can reactivate and sometimes cause retinitis, affecting eyesight.
Tuberculosis (caused by Mycobacterium tuberculosis) has been on the rise in the wake of AIDS, such that some call it a co-epidemic. M. tuberculosis causes a respiratory infection (formerly called consumption) that is spread by inhalation. As a result, unlike HIV, behavior modification is less likely to reduce one's chances of exposure. The bacteria, which have an unusually waxy cell wall, survive well in the environment. M. tuberculosis reproduces inside macrophages found in the lung, and stimulates the production of aggregates of immune cells and connective tissue, called tubercles. Viable organisms can be walled off within such structures for decades, only to become reactivated when a person becomes compromised. Most tuberculosis in AIDS patients results from reactivated infections. AIDS patients suffer not only from respiratory infection but also from disseminated tuberculosis, which can involve the lymphatic system, peritoneum, meninges, urogenital system, or digestive tract. Antibiotic-resistant mycobacteria are also contributing to the rise of tuberculosis, so that second- and third-line drugs must often be used. And because treatments are prolonged, lasting as long as a year, patients sometimes do not complete therapy appropriately. Mycobacteria other than M. tuberculosis, particularly M. avium-intracellulare (MAC), also affect AIDS patients.
Why Do Some Individuals Never Get AIDS?
Despite repeated exposure, some individuals never become infected with HIV. These individuals often have unusual helper T cells with a less-efficient variant of the coreceptor CCR5, which is necessary for viral entry into helper T cells. (See the Human Evolution unit.)
There are also individuals who become infected, but do not progress to AIDS. These long-term survivors, or long-term non-progressors, include individuals who have been AIDS-free as long as eighteen years after infection. A variety of factors may be responsible; for example, infection with less-virulent viruses. Some long-term non-progressors seem to have CD8 cells, which are particularly adept at curtailing HIV infection. (In most AIDS patients CD8 cells become less active.) Several investigators, including Jay Levy (University of California, San Francisco), are evaluating the CD8 cells of long-term survivors to see of they secrete an antiviral protein or proteins that may act against HIV.
Genetic Variation Among HIV
There are five major subtypes of HIV, designated A through E. Different subtypes predominate in different geographical areas. For example, subtype B is more common in North America. In contrast, subtype C predominates in sub-Saharan Africa. Considerable variation within a given subtype also exists. In fact, any given individual infected with HIV will harbor multiple variants of the virus. HIV makes many mistakes as is copies its viral RNA to the DNA that integrates into the host's chromosome. Because of its sloppy copying of reverse transcriptase, HIV's mutation rate is high, causing great variability. This large number of variants makes the virus more difficult to treat and hinders vaccine development. In addition, because of its rapid rate of evolution, even within a single individual, HIV can quickly evolve resistance to the drugs the individual is taking to combat the virus.