Chapter 2
Definition, Symptoms, and Transmittal

A DEFINITION OF AIDS

The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, a branch of the U.S. Public Health Service, is the federal government's clearing-house, research center, and monitoring agency for all infectious diseases, including HIV/AIDS. The CDC tracks the diseases in the United States and notifies health officials of their occurrence via Morbidity and Mortality Weekly Report notices and a Web site that is updated frequently.

The CDC defines AIDS as a specific group of diseases or conditions that are indicative of severe immunosuppression related to infection with HIV. The health agency first outlined a surveillance (a constant observation of a process) case definition in 1982, then revised it in 1983, 1985, 1987, 1993, and again in 2000 as knowledge about HIV infection increased and additional severe and common symptoms were included in the definitions. The January 1, 1993, definition emphasized the clinical importance of the CD4+ T cell count and included the addition of three clinical conditions.

THE 1993 CLASSIFICATION REVISION AND EXPANDED SURVEILLANCE CASE DEFINITION

In 1991 the CDC released a draft of the document that would become the 1993 Revised Classification for HIV Infection and Expanded AIDS Surveillance Case Definition for Adolescents and Adults. This classification scheme has not been revised in the intervening years and so remains the standard in 2005.

The revision addressed the concerns of many women, their attorneys, and physicians, who had strongly advocated the inclusion of diseases such as pelvic inflammatory disease and vaginal candidiasis as conditions that could precede the development of AIDS, so that women infected with HIV would be included in the revised definition. Advocates cautioned that if the CDC omitted such inclusive criteria, many women would be denied access to disability benefits, necessary treatment, and education.

Reasons for Expanding the Case Definition

The CDC reported three reasons for expanding the AIDS surveillance case definitions:

1. To be consistent with standards of medical care for HIV-infected people. The addition of a measurement for severe immunosuppression—a CD4+ T lymphocyte count of 200 per cubic millimeter or less than 14% of total lymphocytes—is consistent with the standard used to determine clinical and therapeutic treatment of HIV-infected persons. (It is important to note that a person can be HIV infected and not have AIDS.) Some clinicians recommend a conservative approach, that all persons with a count of 500 CD4+ T cells per cubic millimeter or less be given antiretroviral therapy. Others advocate more aggressive treatment and begin antiretroviral therapy as soon as the diagnosis of HIV infection is made. Prophylaxis (prevention treatment) against Pneumocystis carinii pneumonia (PCP), the most common serious opportunistic infection (OI), should be started on patients with a count of 200 CD4+ T cells per cubic millimeter or less.
2. To include people with conditions of major public health importance in the HIV epidemic. The inclusion of HIV-infected people with low CD4+ T cell counts allows the HIV/AIDS surveillance to reflect more accurately the number of people who have severe immunosuppression. These people are in the greatest need of close medical follow-up and are at the greatest risk for many or all of the severe HIV-related illnesses. The addition of three clinical conditions—pulmonary tuberculosis (TB), recurrent pneumonia, and invasive cervical cancer—to the twenty-three already accepted conditions of AIDS surveillance criteria indicates the documented or potential importance of these diseases in the HIV epidemic. The prognoses for both pulmonary TB and cervical cancer are improved with appropriate screening tests and proper follow-up. The third condition, recurrent pneumonia, was included to show the importance of pulmonary infections in the causes of HIV-related diseases and deaths.
3. To simplify the AIDS case-reporting process. The CDC tried to simplify the AIDS case-reporting process by allowing clinicians to report HIV-infected people on the basis of CD4+ T cell counts. Limited staff at outpatient clinics and the increasing proportion of AIDS cases necessitated the use of a simplified AIDS surveillance case definition.

New Definition and Classification—Tied to CD4+ Cells

One of the major obstacles in defining AIDS has been that it is not a single disease but several diseases making up a syndrome (a syndrome is a group or pattern of symptoms or abnormalities that are indicative of a certain disease). Newer preventive treatments delay the onset of many diseases such as PCP, which in the past helped to define AIDS. In order to obtain a more realistic picture of the number of AIDS cases, the new classification system emphasized the importance of the CD4+ or helper T cell count.

Based on this, the 1993 definition included all HIV-infected people with a CD4+ T cell count of less than 200 per cubic millimeter or whose CD4+ T cell count was less than 14% of total lymphocytes. Essentially, most people with very low T4 counts would be defined as having AIDS. As shown in Table 2.1, the 1993 classification system was based on three ranges of CD4+ T cell counts (1, 2, 3) and three clinical categories (A, B, C), with nine combinations being possible (A1, A2, A3, B1, B2, B3, C1, C2, C3). People with AIDS-indicator conditions (category C) or those with CD4+ T cell counts of less than 200 per cubic millimeter meet the immunologic criteria for the AIDS surveillance case definition.

Table 2.2 gives a more detailed description of categories A and B, as well as the clinical conditions listed in category C. Note that for classification purposes, once a category C (AIDS indicator) condition occurred, the person remained in category C.

The Impact of the 1993 Definition on Case Reporting

CDC data indicates that expansion of the AIDS surveillance criteria changed both the process of AIDS surveillance and the number of reported cases. During 1993, local, state, and territorial health departments reported 103,500 AIDS cases in the United States among adults and adolescents thirteen years of age and older. This number was twice the 49,016 cases reported in 1992 and likely represented a one-time effect of the 1993 expansion of the AIDS definition. (See Figure 2.1.) The steep increase probably represented the reporting of people who were diagnosed with the newly added conditions before 1993. New reported AIDS cases declined again beginning in 1996 in response to treatments, such as highly active antiretroviral therapy (HAART), that slowed the progression from HIV infection to AIDS. During 1998–1999 the decline in the incidence of AIDS began to level. From 1999 to 2001 essentially no change (or a very slight increase) occurred. But from 2001 through 2003 the number of reported cases again rose, albeit modestly. (See Figure 2.1.)

THE 2000 REVISED SURVEILLANCE CASE DEFINITION

On December 10, 1999, the CDC released a revised surveillance case definition, updating the definition for HIV infection implemented in 1993. (See Table 2.3.) Effective January 1, 2000, the revision integrated the reporting for adult and pediatric HIV infection and AIDS into a single-case definition. The new definition was based on new data obtained using the more sensitive and specific HIV diagnostic tests that were not yet available at the time of the 1993 revision of the AIDS definition. These newer tests detect HIV DNA or RNA; the earlier tests only detected anti-HIV antibodies. The newer tests allow for HIV detection in nearly all infants age one month or older. Since newborns might not have expressed anti-HIV antibodies—if their immune systems have even matured enough to be capable of antibody expression—they would be negative using an antibody-based test.

Although reporting criteria include recommendations for diagnosing HIV infection, the primary purpose of the original and updated case definitions for HIV and AIDS is public health surveillance as opposed to the diagnosis of individual patients.

DIAGNOSIS AND SYMPTOMS OF AIDS

Only a qualified health professional can diagnose AIDS. To evaluate a patient with a positive HIV test, the health care practitioner performs a complete physical examination and collects the patient's social and family history. Diagnostic laboratory tests are also performed. These tests typically include complete blood count and routine chemistry; CD4+ T cell count; assays (analyses) that measure the amount of HIV-1 RNA in plasma; tuberculin skin tests to detect the presence of the bacterium that causes tuberculosis; and assays for the microbial agents that cause syphilis, toxoplasmosis, and hepatitis B and C. Female patients are screened for cervical cancer using the cervical Papanicolaou ("pap") smear.

HIV infection progresses through a range of stages. Following the establishment of the infection (primary infection) there follows a typically prolonged asymptomatic (symptom-free) period prior to the appearance of symptoms and the deterioration of the patient's health. Among the symptoms that develop are weight loss; malaise; nausea; fever; night sweats; swollen lymph glands; a heavy, persistent, dry cough; easy bruising or unexplained bleeding; watery diarrhea; loss of memory; balance problems; mood changes; blurring or loss of vision; and oral lesions, such as thrush (a fungal infection caused by Candida albicans, which appears as a white coating of the tongue and throat). The infecting virus is basically the same in all infected people in terms of its structure and genetic makeup, but individual reactions to the virus vary greatly. Death is usually the result of the OIs and cancers that arise due to the impaired immune system—not HIV.

Dementia

Prior to the 1987 Case Definition many researchers were reluctant to include dementia as a symptom indicative of AIDS. Some observers cited early studies that showed as many as 40 to 70% of people infected with the virus developed neurological and psychological complications several years before other clinical symptoms, such as weight loss and fever, appeared. This fear led both military and civilian authorities to bar infected people from certain jobs involving public safety, including commercial pilots and bus drivers.

Officials at the World Health Organization (WHO), headquartered in Geneva, Switzerland, and the National Institutes of Health (NIH) in Bethesda, Maryland, jointly found these estimates to be false. They reported that although neurological complications are common in the later stages of AIDS, dementia is rarely diagnosed in asymptomatic HIV-infected persons, affecting fewer than 1% of those infected with HIV who have not yet developed AIDS.

A number of research studies were initiated in the 1990s to determine conclusively the link (if any) between dementia and the subsequent diagnosis of AIDS. The data from studies conducted by the U.S. Air Force, a joint effort by the CDC and the San Francisco Health Department, and the Multicenter AIDS Cohort Study of men who have sex with other men in Baltimore, Chicago, Los Angeles, and Pittsburgh (sponsored by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute) confirmed that the 40 to 70% frequency rate of dementia for HIV-infected people was far higher than the actual rate. One explanation for the higher figures reported into the 1980s is that the data came from centers to which AIDS patients with dementia had been referred for treatment. Put another way, the sample population was skewed toward the increased prevalence of dementia.

HIV-associated dementia (also called AIDS dementia complex) is now recognized as a declining cognitive (thinking) function that generally occurs in the late stages of HIV infection. The dementia is caused directly by the destruction of brain cells by the infecting HIV and is different from the forgetfulness and difficulty in concentrating that can be by-products of depression and fatigue.

From HIV to AIDS

Through 2004 the average amount of time from the initial HIV infection to the development of AIDS was eleven years. Still, some patients are HIV-positive for up to twenty years before developing AIDS. The survival time after an AIDS diagnosis has markedly increased since the 1980s. More than two decades ago, death normally followed within two years of diagnosis. But medical developments during the 1980s and 1990s, such as the use of HAART, have significantly increased the life expectancy of AIDS patients.

THE EARLY STAGE

While the timing and progression of HIV infection vary among people, the disease follows a basic pattern. In the beginning of the early stage, shortly after the virus has entered the bloodstream, the T4 cell count is normal (around 1,000 per cubic milli-meter). The virus is undetectable at this stage using assays that are geared to detect the presence of anti-HIV antibodies. The antibody assays can remain negative for up to six weeks. In unusual cases antibodies may remain undetectable for a year or more. Even after testing positive for the virus, or for the presence of the antiviral antibodies, many people remain asymptomatic (showing no symptoms) for years. These people may develop a disorder similar to infectious mononucleosis with fatigue, fever, swollen glands, and possibly a rash. Often, these symptoms disappear within a few weeks and a connection with HIV infection is not made. Throughout this time, however, the virus is multiplying and destroying healthy cells. Most people continue to feel fine, though some may have chronically swollen lymph nodes. This stage usually lasts about five years.

THE MIDDLE STAGE

By the middle stage of infection, the CD4+ T cell count is reduced by half, to around 500 per cubic millimeter. Even with this physiological change, many people may still be asymptomatic. As the infection advances, skin tests will likely show that cellmediated immunity, a form of immunological defense, is disintegrating. The deterioration of the immune system has begun. This stage can also last up to five years.

In the 1980s a drug called azidothymidine (AZT; now also called zidovudine), which had failed to fulfill its early potential as an anticancer compound, garnered a lot of publicity when it was shown to help slow the attachment of HIV to host cells. AZT delayed the onset of symptoms and extended this middle stage of the infection. Disappointingly, AZT's benefits proved to be temporary, as HIV mutated to counteract the effect of the drug. The drug is still used today in conjunction with other medicines, and some studies suggest that people who receive AZT may develop AIDS later than those who do not take it.

Newer and more promising drugs have since been developed, in particular the protease inhibitors, which prevent the virus from destructively degrading cell protein. Protease inhibitors were licensed for use by the U.S. Food and Drug Administration (FDA) in December 1995.

Structured treatment interruptions (STIs), initially proposed in the late 1990s, in which the multiple drug therapy patients receive is stopped for short periods of time, have also shown promise. But the disastrous consequences that have resulted from patients taking self-initiated "drug holidays" underscore the importance of gaining a physician's approval for being on an STI program. As of 2005 it remains unclear whether STI truly does help suppress or delay AIDS symptoms.

THE LATE STAGE

The third and final stage of HIV infection is reached when the CD4+ T cell count per cubic millimeter drops to 200 or below. Though many patients are still asymptomatic at this point, the functioning of the immune system has by now been markedly weakened. The body is far less able to defend itself from invasion. As a consequence, the risk of infection due to opportunistic bacteria, viruses, fungi, and parasites and the possibility of cancer increase dramatically. In order to prevent PCP, one of the most common OIs, patients are usually treated with antibiotics during this stage.

At the onset of the late stage, patients may experience weight loss, diarrhea, lethargy, and recurring fever. Skin and mucous membrane infections increase. Oral fungal infections such as thrush and a chronic infection caused by the herpes simplex virus are common.

As the late stage progresses, the immune system begins to collapse rapidly. OIs move deeper into the body. It is not uncommon for a parasitic infection called toxoplasmosis to attack the brain, while the cryptococcosis fungus attacks the nervous system, liver, bones, and skin. Cytomegalovirus can cause pneumonia, encephalitis, and retinitis. The latter, an inflammation of the retina, can cause blindness. Many other infections can occur. The consequences and complications of compromised immune function are numerous, and death becomes a matter of time. The average survival rate, once the late stage has been reached, is two years.

TRANSMISSION OF HIV

When AIDS was first discovered, it was often compared to the Black Death of the fourteenth century, in terms of the public panic surrounding the disease and its possible spread. The comparison has not proved to be valid. The bacterium that caused the Black Death (and which still causes bubonic plague) is very contagious, being readily transmitted via food, water, and air. HIV is not nearly as contagious. Moreover, by observing precautions that prevent the sharing of bodily fluids, the transmission of HIV can be almost entirely prevented.

The accumulated knowledge of more than twenty years of research and observations have definitively established that the HIV infection can only be transmitted by the following routes:

• Oral, anal, or vaginal sex with an infected person. Sexual intercourse—particularly heterosexual sex—is the most common mode of HIV transmission.
• Sharing drug needles or syringes with an infected person.
• Maternal transmission to a baby perinatally (at the time of birth) and possibly through breast milk.
• Transplantation of HIV-infected organs or transfusion of infected bodily fluids, such as blood or blood products. In the mid-1980s the transfusion of HIV-infected blood caused thousands of cases of AIDS and led to many deaths in separate incidents in Europe, the United States, and Canada. The blood agencies of the affected countries have revamped their blood-testing policies so that molecular assay techniques, which detect HIV genetic material, are used to screen every donated blood sample.

Confirming the involvement of bodily fluids in HIV transmission, high concentrations of HIV have been found in blood, semen, and cerebrospinal fluid. Not all body fluids seem to be involved, since HIV concentrations one thousand times less have been found in saliva, tears, vaginal secretions, breast milk, and feces. But there have been no reports of HIV transmission from saliva, tears, or human bites. In fact, in 1995 the National Institute of Dental Research in Bethesda, Maryland, reported that a small protein found in human saliva actually blocks the virus from entering the system.

Casual Contact

While HIV is an infectious, contagious disease, it is not spread in the same manner as a common cold or chicken pox. It is not spread by sneezing or coughing, as are airborne illnesses. HIV is not spread by sharing a bathroom, swimming in a pool, or by hugging or shaking hands. Studies of family members who lived with and cared for AIDS patients have not found definitive evidence that anyone has become infected through casual contact. Still, myths abound. To combat misinformation, the U.S. Surgeon General's office and public health education initiatives continue to stress that HIV is not spread by:

• Bites from mosquitoes or other insects.
• Bites from animals.
• Food handled, prepared, or served by HIV-infected people.
• Forks, spoons, knives, or drinking glasses used by HIV-infected people.
• Chairs previously occupied by people with HIV.
• Casual contact such as touching, hugging, or kissing a person who is HIV-positive (open-mouth kissing with a person who is HIV-positive is not recommended because of potential exposure to blood).

Donating Blood

Health officials agree that donating blood poses no danger of HIV infection for the donors. The needles used to draw blood from donors are new and are thrown away after one use. Contact with HIV from donating blood is therefore impossible.

SAFETY OF BLOOD AND TRANSPLANT PROCEDURES

According to the CDC, more than 400 American institutions either bank or commercially process one or more human tissues, organs, or fluids. Approximately one hundred eye banks, 125 bone banks, one hundred semen banks, ninety-nine bone marrow transplant centers, and seven human milk banks operate in the United States. Additionally, the number of hospitals that store bone and the number of physicians' offices that store semen is undetermined and likely large.

To safeguard the nation's transplant recipients, the CDC suggests that all donors of blood products, tissue, and organs be screened and tested. The recommendations include screening for behaviors—risk factors—associated with the acquisition of HIV infection, a physical examination for signs and symptoms related to HIV infection, and laboratory screening for antibodies to HIV. It is important to remember that the CDC does not regulate medical protocol; its main function is to offer health care guidelines and information to the nation and its health care providers.

The U.S. Blood Supply

Before HIV-antibody testing began in 1985, it is estimated that 70% of hemophiliacs (people with inherited bleeding disorders) who received blood products were given tainted blood-clotting factor (a concentrate of blood used to stem bleeding) and were therefore infected with HIV. Approximately ten thousand of these patients developed AIDS and, according to the National Hemophilia Foundation, most have died.

Widespread use of two blood-screening tests, both of which are also used on plasma and other blood products, has strengthened the safety of the U.S. blood and plasma supply. Since 1992 the Public Health Service, an arm of the U.S. Department of Health and Human Services, has required that all blood and plasma donations be screened for the rare HIV-2 antibody, as well as the more common HIV-1 antibody.

In 2001 the FDA approved the first nucleic acid test (NAT) system to screen plasma donors for HIV. Rather than relying on the identification of antigens or antibodies, the new test provides extremely sensitive detection of RNA from HIV-1. Even with the new test, however, there is still some risk due to the "window period" during which a person who has acquired the HIV-1 infection may still test negative. For HIV-1 antigen and antibody detection, the window period is sixteen and twenty-two days, respectively, following infection. NAT systems reduce the window period to twelve days. Put another way, anyone who is infected with HIV and who donates blood more than twelve days after exposure to the virus will register HIV-positive.

Of the twelve million units of blood donated annually in the United States, the CDC estimates that between thirty-two and forty-nine units are potentially infectious. While the U.S. blood supply is considered safe, blood banks across the country nonetheless encourage individuals concerned about tainted blood to bank their own blood for possible future use.

Foreign Blood Supplies

HIV infection from contaminated blood has been much more common in other countries. In July 1998 a French court ruled that a former prime minister and two former cabinet members would be tried on charges that they allowed HIV-contaminated blood to be used for transfusions during 1984 and 1985. Relatives of the patients argued that the French government had refused American technology that would have detected antibodies in the tainted blood in favor of a French procedure in development. Estimates vary, but as many as four thousand people acquired HIV as a result of this action. An estimated 1,250 hemophiliacs were infected and at least 400 of them, including many children, have since died of AIDS. The former French officials, Prime Minister Laurent Fabius, Social Affairs Minister Georgina Dufoix, and Health Minister Edmond Herve, faced charges of involuntary homicide and went to trial in 1999. Herve was convicted without a penalty and Dufoix and Fabius were acquitted. The tragedy resulted in the overhaul of the blood supply and donation networks in France.

In 1995 the WHO reported that three thousand children in Romania—home to thousands of abandoned babies left in squalid institutions after the fall of Romanian dictator Nicolae Ceausescu—were infected by contaminated blood and syringes in the late 1980s. The WHO estimates that one thousand of those children have died. In 1998 Romania had more than half of the juvenile AIDS cases in Europe; more than 90% of the country's AIDS cases were among children. The Romanian Health Ministry faced litigation for causing the spread of HIV.

In 1995 the owner of a German drug laboratory was charged with nearly six thousand counts of murder or attempted murder for selling HIV-tainted blood products to German hospitals in 1987. Not all of the six thousand batches distributed had been tested for HIV. Testing has been mandatory in Germany since 1986.

The Canadian blood collection, testing, and distribution system was completely overhauled in the wake of the distribution of HIV-contaminated blood before 1986 (when HIV testing was not yet available) and after 1990 (when more sensitive tests that could detect HIV were available, but which were not immediately used by the Canadian blood collection service). In 2001 Canada's Supreme Court ruled that the negligence of the blood agency during the early years of the AIDS crisis entitled several thousand affected Canadians to a $1.2 billion federal-provincial government compensation offer. Legal wrangling in the intervening years has delayed the implementation of the court's ruling. As of June 2005, those affected by the tainted blood have yet to be financially compensated.

Organ and Tissue Transplants

In several instances HIV has been transmitted through organ (kidney, liver, heart, lung, and pancreas) and other tissue transplants. The risk of such transmission is low simply because there are far fewer transplant cases than blood transfusions.

In 1994 the FDA began regulating the sale of bone, skin, corneas, cartilage, tendons, and similar nonblood vessel-bearing tissues used for transplants. The FDA requires that all procurement agencies conduct behavioral screening and infectious-disease (HIV-1, HIV-2, hepatitis B virus, and hepatitis C virus) testing of donors.

TESTING PEOPLE FOR HIV

A person infected with HIV produces antibodies specific to the virus as part of the body's immune response to the invader. While the antibodies are not enough to successfully fight HIV, they are of diagnostic value, as they can indicate the presence of the virus.

Antibody-based HIV testing is done, rather than a direct test for the virus itself, because it is too difficult to isolate the virus from the blood. Testing serves to determine if there is a viral infection in donated blood, tissues, or organs. This protects the recipients of the donated material and can be used to identify HIV-infected donors.

An antibody-based test cannot detect all HIV-positive blood. It can typically take between four and twelve weeks following HIV infection for antibodies to appear, although in rare cases this period can be up to one year. This interval between acquisition of the virus and the appearance of antibodies is called the "window period." The introduction of tests that detect the viral nucleic acid rather than the HIV antibodies has markedly increased the detection sensitivity of blood screening. Still, even nucleic acid detection has a window period, albeit a shorter one, of about twelve days.

The fact that detection is not absolute from the moment of HIV infection means that the possibility exists that some HIV-infected donors may not be diagnosed and their blood may enter the nation's blood supply. However, the number of predicted contaminated blood samples is extremely small. To try to further reduce the chances of contaminated blood entering the blood supply, blood banks routinely question potential donors about high-risk behaviors. Any donor whose behavior might indicate an increased risk of HIV infection (such as intravenous drug use or male-to-male sex) is automatically excluded from donating blood.

Diagnostic Tools for HIV Antibodies

Two tests commonly used to detect HIV antibodies are believed to be about 99% reliable. These tests are the enzyme-linked immunosorbent assay (ELISA) and the Western blot.

ELISA, introduced in 1985, is a test designed for screening rather than diagnosing. The assay uses purified HIV antigens to probe for the presence of complimentary antibodies in a sample such as blood. If anti-HIV anti-bodies are present in the sample, they attach themselves to the viral proteins that have been immobilized on a plastic surface. A second antibody that has been raised against the anti-HIV antibody (antibodies are proteins too, and so can themselves function as antigens, stimulating the formation of antibodies) is bound to the anti-HIV antibodies. The second antibody also contains a chemical that can be made to change color. The color change reveals the presence of the anti-HIV antibody. If no color change appears, no anti-HIV antibody is present in the blood sample. This test is reliable, simple to conduct, and inexpensive.

The Western blot, introduced in 1987, is a confirmatory test. This means the test is commonly used to verify the results of the less-specific assays. The Western blot technique separates the various HIV proteins from one another, based on their speed of movement through a gel under the influence of electricity. The separated proteins are transferred from the gel to a membrane made of a material such as nitrocellulose. When the nitrocellulose is exposed to a blood sample, antibodies that recognize one of the proteins on the nitrocellulose will bind to the particular protein. As with ELISA, a color reaction can be induced to indicate the site of the bound antibodies. The Western blot provides a positive, negative, or intermediate result. The presence of three or more of the color bands confirms an HIV infection. If fewer—one or two—bands appear, the test is considered intermediate and retesting is performed six months later. If no color bands appear, the test is considered negative with no HIV present, though many people who test negative also repeat the test six months later.

Urine Tests

In June 1998 the FDA approved a new, urine-based diagnostic kit for HIV marketed by Calypte Biomedical Corporation that does not require confirmation by blood test. Urine tests are easier to use and cost less than blood tests for health care providers. According to the National Institutes of Health, there is no evidence that HIV is spread through urine. Therefore, the chances of accidental infection through needle sticks or handling of samples are lessened. The urine test and its urine-based confirmation test, like most blood tests, recognize the existence of antibodies, not the actual virus.

The test is marketed to life insurance companies, clinical laboratories, public health agencies, the military, immigration authorities, and the criminal justice system. In June 2000 Calypte announced its partnership with the Chinese National Center for AIDS Prevention and Control (NCAIDS) to distribute the first HIV-1 antibody urine test in the People's Republic of China. NCAIDS estimates that the total number of HIV infections in China could rise to as high as ten million before 2010 if proper countermeasures are not taken.

A clinical trial of Calypte's diagnostic kit for HIV was conducted by the Chinese CDC, involving approximately fifteen hundred people, some known to be HIV-positive and some uninfected. Results released in early September 2005 indicated the kits were successful, and Calypte planned on submitting the kits for approval in China, which plans to use the product as the exclusive noninvasive method of testing for HIV.

Home Testing

In 1997 a recently approved home HIV test was analyzed in a multisite test study involving 1,255 people. Test participants registered anonymously by telephone with a testing laboratory. The subjects simply stuck a finger to draw blood and mailed the dried blood sample on filter paper to the laboratory. There, a phlebotomist (a health worker who draws blood by syringe or needle) matched the results with blood that had been drawn earlier from the patient's vein in the traditional manner. Results of the test were obtained by calling a toll-free telephone number. Negative results were given by recorded message. For positive results, a trained counselor offered callers follow-up information and counseling. Of the 1,255 people who participated, 1,104 participants called in to check their test results. For those participants the home test matched the phlebotomy results exactly.

Although there is no new technology involved in home testing, it offers the advantages of privacy and ease of use. Critics of home testing point out that it is expensive; a kit costs $40 to $60 and may be prohibitively expensive for poorer populations—for whom such a test is most needed. Critics also question the impersonal practice of relaying HIV-positive results and follow-up counseling by telephone.

As of 2005 the FDA had approved only the Home Access Express HIV Test System, produced by the Home Access Health Corporation. The FDA warned that non-approved home HIV tests could produce inaccurate results. When Home Access testing kits were made available over the counter, rather than by physician prescription, in 1998, sales at two retail drugstore chains that were surveyed increased 360 to 570%.

Quick-Response Tests

During the mid- to late 1990s, the CDC recommended the development of a new HIV test that would give results instantly. The CDC hoped that this would encourage people to learn the results of their tests. Currently, nearly seven hundred thousand people each year do not follow up to learn their test results. The CDC stresses the importance of obtaining results quickly. They contend that people are not only more likely to take a test that gives results instantly, but will also benefit from the opportunity to learn they are infected before their immune systems have been seriously damaged. Furthermore, rapid results may lead to earlier, more effective treatment and might reduce transmission of the virus.

The FDA has approved a number of rapid tests designed for use in clinics in the United States. The first test to be approved is manufactured by Murex Diagnostics Inc. of Norcross, Georgia. This test detects the presence of HIV antibody in about ten minutes. The test is as accurate as the standard Western blot test. But because the Western blot test also looks for protein bands, this test remains the absolute antibody-based indicator of HIV.

In late 2002 the FDA announced approval of another blood-based antibody test (OraQuick Rapid HIV-1 by OraSure Technologies Inc., Bethlehem, Pennsylvania) for use. As of 2005 the test, which produces results within about ten minutes, is not licensed for home use and can only be performed in a clinical setting. But the fact that the test does not require any specialized equipment or refrigeration offers the possibility of home use in the future.

Another similar rapid test kit, developed and manufactured by MedMira Inc. of Halifax, Canada, was granted FDA approval in April 2003 for sale in the United States. The kit is also approved in China, where HIV infection rates dramatically increased in the early 2000s.

Rapid HIV tests are used more frequently in other countries, such as China. In developing countries, for example, quick-response tests are used to screen blood before transfusions, to screen pregnant women so medical interventions can be given to prevent mother-to-child transmission of the virus, and in rural clinics.

Test Tracks HIV/AIDS Progression

In June 1996 the FDA approved a test to help determine how fast an HIV infection progressed to full-blown AIDS. Developed by Roche Diagnostic Systems Inc., the Amplicor HIV-1 monitor test is not intended to screen for HIV or to confirm an HIV diagnosis. Instead, the test detects the amount of HIV in the blood (the viral load) by measuring HIV genetic material. An increased viral load indicates the advancement of the infection toward AIDS and an increasing predisposition to the development of OIs. The test is based on a technique developed in 1984 called the polymerase chain reaction (PCR). PCR uses a heat-resistant bacterial enzyme to amplify the copies of target stretches of genetic material to detectable amounts. The process can be completed in less than one hour. This test was the first PCR-based test to be approved.

In 1997 FDA approval was granted to expand the use of the test as an aid in managing HIV in patients under-going antiretroviral therapy. In 1999 a more sensitive version of the test became available. As of 2005 the test was used in eight out of ten clinical labs worldwide, according to the manufacturer.