HIV Tests, Symptoms, Signs, and Stages of Infection

Untreated infection with HIV progresses over time and gradually impairs specific parts of the immune system, especially by destroying the white blood cells known as CD4 lymphocyte cells. This progression is described as occurring in stages. All stages require laboratory confirmation of HIV infection.

There are multiple different staging systems. For example, the Centers for Disease Control and Prevention case definition uses a staging system based on how much damage has been done to the immune system:

• Stage 1 disease is the earliest phase. Stage 1 has no unusual infections or cancers or other conditions that would be associated with AIDS. In other words, stage 1 disease has no "AIDS-defining conditions" (see below). Although blood tests are positive for HIV, the CD4 cell count is at least 500 cells per microliter of blood (or >29% of all lymphocytes).
• Stage 2 disease occurs when the CD4 count is between 200-499 cells per microliter (14%-28% of all lymphocytes), but again there are no AIDS-defining conditions present.
• Stage 3 disease is synonymous with AIDS and is the most severe stage. There are two ways of diagnosing stage 3 disease: either by CD4 counts below 200 cells per microliter (<14% of lymphocytes) or through documentation of an AIDS-defining condition.

Another way to conceptualize HIV is according to the characteristics or clinical manifestations: acute infection, clinical latency, or AIDS.

• Acute infection: Two to four weeks after infection with HIV, the patient can experience an acute illness, often described as "the worst flu ever." This is called acute retroviral syndrome (ARS) or primary HIV infection, and it is caused by the body's natural response to the HIV infection. Not all newly infected people develop ARS, however -- and it can take up to three months for it to appear. During this period of infection, large amounts of virus are being produced. The virus uses CD4 cells to replicate and destroys them in the process. Because of this, the CD4 count can fall rapidly. Eventually, the immune response will begin to bring the level of virus in the body back down to a level called a "viral set point," which is a relatively stable level of virus in the body. At this point, the CD4 count begins to increase, but it may not return to pre-infection levels. The human immune response suppresses the virus but does not eliminate it from the body.
• Clinical latency: After the acute stage of HIV infection, the disease moves into a stage called clinical latency. This period is sometimes called asymptomatic HIV infection or chronic HIV infection. During this phase, HIV reproduces at very low levels, although it is still active. In this state, infected people may be able to maintain an undetectable viral load and a healthy CD4 cell count without the use of medication for a time. There are usually few if any symptoms. This period can last up to eight years or longer. However, some people progress through this phase faster than others. It is important to remember that people are still able to transmit HIV to others during this phase. Toward the middle and end of this period, the viral load begins to rise and the CD4 cell count begins to drop. As this happens, infected people may begin to have constitutional symptoms such as fatigue and other nonspecific symptoms.
• AIDS: As the number of CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/cubic milliliter), people will be diagnosed as having AIDS. Normal CD4 counts are between 500 and 1,600 cells per cubic milliliter. This is the stage of infection that occurs when the immune system is badly damaged and patients become vulnerable to opportunistic infections. Without treatment, people who are diagnosed with AIDS typically survive about three years. Once someone has a dangerous opportunistic infection, life expectancy falls to about one year.

AIDS-defining conditions in an HIV-infected person include the following:

• Candidiasis of bronchi, trachea, lungs, or esophagus
• Cervical cancer, invasive
• Disseminated or extrapulmonary coccidioidomycosis or Cryptococcus
• Chronic intestinal cryptosporidiosis or isosporiasis
• Cytomegalovirus disease of the retina or an unusual site (other than liver, spleen, or nodes)
• HIV encephalopathy
• Herpes simplex that does not heal or that occurs in the lungs or esophagus
• Histoplasmosis that is disseminated or extrapulmonary
• Kaposi's sarcoma
• Lymphoid interstitial pneumonia and/or pulmonary lymphoid hyperplasia*
• Selected lymphomas including Burkitt's, immunoblastic, or arising in the brain
• Disseminated or extrapulmonary Mycobacterium avium-intracellulare complex or Mycobacterium kansasii, or other species of mycobacterium
• Mycobacterium tuberculosis infection
• Pneumocystis jirovecii pneumonia
• Recurrent bacterial pneumonia
• Progressive multifocal leukoencephalopathy
• Recurrent or multiple bacterial infections
• Recurrent Salmonella septicemia
• Toxoplasmosis of brain
• Wasting syndrome associated with HIV infection

SLIDESHOW

A Timeline of the HIV/AIDS Pandemic See Slideshow

As described above, although some people have no symptoms in the early weeks after acquiring HIV, between one-third and one-half will experience symptoms of fatigue, achiness, sore throat, enlarged lymph nodes, and loss of appetite. Mouth symptoms might include thrush or mouth sores. Fever, neck stiffness, headache, and rash may occur. Symptoms in women may include recurrent vaginal yeast infections. This acute retroviral illness (ARS) usually starts one to six weeks after infection and lasts approximately two weeks. Some people experience ARS as long as three months after initial infection. During this time, the blood is teeming with HIV and the CD4 lymphocyte count is reduced, creating susceptibility to unusual infections. Antibodies against the virus are beginning to form, the viral set point is established, and the infected person becomes asymptomatic, although some may have persistent moderately enlarged lymph nodes. As disease advances, other conditions may appear. Although not specific to HIV, symptoms in women may include recurrent vaginal yeast infections, and symptoms in men who have receptive anal sex may include severe or recurrent herpes infections. Mouth problems might include thrush or oral hairy leukoplakia, which is due to infection with the Epstein-Barr virus.

If patients are not treated, they progress to stage 3 in approximately 10 years. Patients in stage 3 have immune systems that are so impaired that they create susceptibility to unusual infections or cancers. These AIDS-defining conditions are listed above. Symptoms depend on the type of infection or cancer that is acquired. For example, patients with pneumonia may have shortness of breath and cough or wheezing. Occasionally, HIV may cause an AIDS-defining condition directly through intense infection of the brain, which causes confusion and encephalopathy.

There are two main ways to diagnose HIV infection: detecting the virus directly or detecting antibodies that are made against the virus.

The body makes antibodies to try to fight HIV, although the antibodies cannot eradicate the virus. Antibody testing is often done in two parts. First a sensitive screening test is performed on the blood. If the screening test is positive, a second test is done to confirm that HIV antibodies are present. The types of tests have varied over the years. At first, the screening test used an enzyme-linked immunoassay (ELISA) with confirmatory testing by Western blot. This strategy did not test for HIV-2, sometimes misclassified HIV-2 infection, missed very early infections where antibody had not yet been produced, and sometimes produced indeterminate results. Scientists developed newer tests to address these issues. Other tests took hours or days to return results, requiring people to return to the clinic. Rapid HIV tests (such as Clearview) were developed that could provide results during the initial visit. Some tests can be done at home without the need for a clinic visit. For a self-test or home-test, the person buys a kit (for example, OraQuick), swabs the inside of their cheek, places the swab in the supplied fluid, and reads the results in a test window. Positive results indicate the need to visit a clinic for confirmatory testing.

New fourth-generation tests combine viral detection and antibody detection. Viral detection is done by testing for a component of the virus known as p24 antigen. The fourth-generation tests also detect antibodies against both HIV-1 and the less common HIV-2, as well as antibodies that are made in the early stage of disease (IgM) and in chronic disease (IgG). Draft guidelines from the Centers for Disease Control and Prevention (CDC) in 2012 recommend using FDA-approved fourth-generation tests as the first step in diagnosis. If the fourth-generation test is positive, additional antibody tests are done to differentiate HIV-1 from HIV-2 and to measure viral load.

Viral load is measured by testing the amount of viral RNA in the blood. It can be useful for patients who have confusing test results, such as a positive fourth-generation test but negative or indeterminate individual tests for HIV-1 and HIV-2. In these cases, if viral RNA is detected, the diagnosis of HIV is made. If viral RNA tests are negative, it raises the possibility that the fourth-generation test result was not correct. Viral load is also used to monitor the success of treatment for infected patients. Viral load can also be useful in diagnosing acute retroviral illness because HIV antibodies take time to reach detectable levels.

The CDC recommends HIV testing at least once for all people between the ages of 13 and 64. People at high risk, such as those who use illicit injectable drugs or who have multiple sexual partners, should get tested more frequently. All pregnant women should be tested because effective treatment can dramatically reduce the risk of transmission to the unborn child. Victims of sexual assault should be tested. People who are diagnosed with another sexually transmitted disease, such as syphilis, chlamydia, or gonorrhea, should be tested for HIV as well.