Human Immunodeficiency Virus (HIV) Diagnosis

  • Diagnosis

    Human immunodeficiency virus (HIV) suppresses the immune system's ability to fight infection and disease. HIV was first identified in the early 1980s when doctors and public health officials began to notice clusters of previously unusual infections. The virus targets white blood cells in the immune system known as helper T cells (or CD4 cells), thus impairing the body's ability to fight infections. People infected with the HIV virus will gradually develop lower levels of CD4 cells and higher levels of HIV virus in their blood. CD4 cell levels are an important marker of HIV disease severity. The introduction and use of drug regimens to combat HIV infection has meant that many HIV-infected people with access to these drugs have a much-increased life expectancy than ever before.

    HIV infection progresses through these stages: viral transmission, primary infection, seroconversion, clinical latent period with or without persistent generalized lymphadenopathy, early symptomatic disease, AIDS and advanced HIV infection.

    • Viral transmission. This involves the introduction of the HIV virus from an already-infected person to someone who was not previously infected.
    • Primary infection. This is the stage in which HIV first enters the body and begins reproducing itself. Primary infection may be accompanied by the sudden onset of flulike symptoms such as fever, joint pain, swollen lymph nodes, sore throat, mouth sores, nausea, diarrhea, and headache. Some people experience no symptoms at all. Symptoms generally occur two to four weeks after viral transmission occurs.
    • Seroconversion. Seroconversion means that the virus will show up on blood tests. Most people exposed to HIV will seroconvert within four to 10 weeks, although it can take up to 6 months for some people.
    • Asymptomatic disease. During this stage, which typically lasts from two to 10 years, HIV becomes established in the body, but does not cause symptoms. The number of CD4 cells in the blood begins a gradual decline, starting from around 1,000 cells per milliliter (mL) of blood to around 500 cells per mL.
    • Symptomatic disease. When the CD4 count drops to between 200 and 500 cells per mL, patients may develop symptoms such as swollen glands, fatigue, unexplained weight loss, and fever. Infections that rarely occur in people with healthy immune systems also begin to appear.
    • AIDS. AIDS isn't a single disease, but rather a group of symptoms or illnesses that occur together. AIDS has been defined by the U.S. Centers for Disease Control and Prevention (CDC) as occurring in a person who:

      • Has a laboratory-documented HIV infection
      • Has a CD4 count less than 200 cells per mL of blood
      • Has had one or more infections or types of cancer that do not occur regularly in the general population.These infections include Candida (a yeast infection) of the esophagus or lungs, disseminated tuberculosis, PCP pneumonia, several bouts of bacterial pneumonia, and extrapulmonary coccidiomycosis and histoplasmosis. The types of cancer include invasive cervical cancer, Kaposi's sarcoma, and certain types of lymphoma. People without HIV develop cervical cancer and lymphoma, but anyone known to be infected with HIV who then develops one of these conditions is considered to have AIDS.

    • Advanced AIDS. Anyone who has AIDS with a CD4 count less than 50 cells per mL has advanced AIDS. Survival at this stage is generally only 12 -18 months in people not taking medications to treat AIDS.

    While the majority of people who contract HIV will ultimately develop AIDS, the time between initial HIV infection and the development of AIDS varies widely. Historically, most HIV-positive people develop AIDS within 10 to 11 years after infection; however, some people have lived with HIV for 15 years or more without symptoms. There currently is no cure for AIDS, though scientists are trying to develop a vaccine to prevent its spread. Highly active antiretroviral therapy (HAART), available in the developed world since 1996, has greatly prolonged the life expectancy of people living with AIDS who have access to this treatment.

    HIV is spread primarily via contact with bodily fluids such as blood, semen, and vaginal secretions. HIV can also be spread from an infected mother to her fetus and via transplantation of infected organs. HIV cannot survive outside of the body for very long, and can only be transmitted through contact in which bodily fluids are exchanged. The primary means of HIV sexual transmission is through vaginal or anal intercourse, but HIV can also be transmitted through oral sex. HIV does not appear to be transmitted through kissing.

    In the early years of the epidemic before effective tests for the virus were available, many people contracted HIV through blood transfusions, or from using blood-clotting factors, such as Factor VIII, used in hemophilia. Today, the risk of getting HIV from the blood supply is very small, particularly in the developed world in which donated blood undergoes rigorous testing. Blood-borne transmission of HIV occurs most commonly among people who share intravenous needles when using illicit drugs. HIV can spread via organ transplant, but rigorous testing of organ donors and the organ supply has greatly reduced the likelihood of this occurrence.

    HIV can be passed from a mother to her child during pregnancy or childbirth, and after birth through breast milk. Viral transmission to the child may occur in the uterus. The risk of transmission is enhanced if there is a prolonged period of time between the rupture of a mother's membranes and the time of delivery. In addition, breast milk contains relatively high levels of HIV, and transmission of the virus from mother to child through breast-feeding has been well-documented. This route of transmission is especially problematic in developing countries where HIV-infected mothers may not have access to affordable, sterile, nutritious infant formula.

    There are no documented cases in which HIV was transmitted through ordinary social contact. HIV transmission is not known to have occurred through touching, kissing, hugging, shaking hands, sharing food, being bitten by an insect, sitting on an infected toilet seat, or working or playing with an infected person.

    During primary HIV infection you may have no symptoms, or may experience a short, flulike illness Table 01. Symptoms of a primary HIV infection, if present, include sore throat, fever, nausea and vomiting, diarrhea, fatigue, swollen glands, muscle aches, headaches, and joint pain. Occasionally, the virus causes meningitis (inflammation of the lining of the nerves and brain) or encephalitis (inflammation of the brain). The symptoms of the initial infection clear up without treatment within a few weeks, and there may be no additional symptoms for 10 years or more.

    Table 1.  Symptoms of HIV Infection

    Symptoms of initial infection Symptoms of later disease
    Sore throat FeverNausea and vomiting Fatigue Swollen lymph nodes Headaches, muscle aches, joint pain Occasionally meningitis or encephalitis Enlarged lymph nodes over several areas of the body Persistent fever, night sweats, or chills Sudden unexplained weight loss Persistent diarrhea Mouth sores Persistent dry cough Persistent oral (thrush) or vaginal yeast infections

    After the primary infection, infected persons will enter an asymptomatic phase. During the asymptomatic phase of HIV infection, the virus becomes established in the body, and a person's CD4 count will decrease. An infected person at this stage will not, however, experience any symptoms for several years.

    When HIV symptoms recur, many different parts of the body may be affected. The most common persistent symptom of HIV infection is often enlarged or sore glands (lymph nodes) in the neck, armpit, and groin. Other symptoms include fatigue, chills, fever, night sweats, skin rash, persistent headache, unexplained weight loss lasting at least one month, diarrhea for several weeks or more, a persistent dry cough, a white coating on the tongue (thrush), Figure 01 or persistent vaginal yeast infections.

    Click to enlarge: Oral Thrush

    Figure 01. Oral Thrush

    In its late stages (AIDS), HIV infection may spread to the central nervous system, causing dementia and other neurological disorders. In some people infected with HIV, the virus causes a cluster of symptoms known as AIDS dementia complex, or HIV encephalopathy. Symptoms of this complex include impaired ability to concentrate, increased forgetfulness, difficulty reading, or increased difficulty performing complex tasks. In addition, the complex may also include behavioral changes such as apathy, and motor difficulties such as unsteady gait, poor balance, and tremors. Late stages may also be characterized by bowel or bladder incontinence.

    Multiple infections and cancer may develop as the immune system weakens Table 02. In addition, people with HIV may develop Kaposi's sarcoma Figure 02, a rare cancer of the blood vessels that manifests as bluish-red nodules on the surface of the skin.

    Click to enlarge: AIDS-related Kaposi's Sarcoma.

    Figure 02. AIDS-related Kaposi's Sarcoma.

    Table 2.  Opportunistic Infections Associated with HIV Infection

    Infection Symptoms
    Latent/minimally symptomatic stage
    Candidiasis Oral yeast infections: white patches on the gums, tongue, or lining of the mouth; pain or difficulty swallowing; loss of appetite. Vaginal yeast infections: burning, itching, discharge.
    Tuberculosis Cough, weight loss, night sweats, fatigue, fever, coughing up blood.
    Herpes simplex infection Painful blisters, ulcers, and/or itching on the lips, anus, or genitals.
    Late stage (AIDS)
    Pneumocystis carinii pneumonia Fever, dry cough, difficulty breathing, weight loss, night sweats, fatigue.
    Cryptococcal meningitis Mild headaches, malaise, fever, nausea, fatigue, loss of appetite, altered mental status.
    Toxoplasmosis Altered mental states, paralysis on one side of the body, seizures, severe headaches, fever.
    Mycobacterium avium complex (MAC) Fever, night sweats, fatigue, weight loss, diarrhea, anemia, abdominal pain, weakness, dizziness, nausea, enlarged glands, enlarged liver and spleen.
    Cytomegalovirus (CMV) infections Blurry vision, pain or difficulty swallowing, fever, diarrhea, abdominal pain, weight loss.
    Esophageal candidiasis Pain or difficulty swallowing.
    Histoplasmosis Fever, weight loss, skin lesions, difficulty breathing, enlarged glands.
    Chronic mucocutaneous herpes Large, painful ulcers and/or itching on the lips, anus, or genitals that won't go away.
    Crytosporidiosis Diarrhea, abdominal cramping, nausea, vomiting, fatigue, gas, weight loss, loss of appetite, constipation, dehydration.

    Engaging in unsafe sexual practices increases your risk of contracting HIV. Unsafe sexual practices include having sex with an HIV-infected person without using latex condoms, having multiple sex partners, and having sex with someone in a high-risk group. High-risk groups include men who have sex with men (MSM), people of either sex who have multiple sex partners, and intravenous drug users.

    Sharing needles for intravenous drug use increases your risk of contracting HIV. HIV is more common among intravenous drug users than among the general population. Sharing needles or intravenous drugs puts you at serious risk of exposure to and infection with HIV. Sharing needles also increases the risk of transmitting other blood-borne pathogens such as hepatitis B and hepatitis C.

    Needlesticks from an HIV-positive source constitute a risk for healthcare workers and others whose jobs bring them in contact with blood or other bodily fluids: 3 in 1,000 needlesticks from an HIV-positive source will result in HIV infection.

    The HIV virus can be transmitted through the blood supply and through blood treatments, such as Factor VIII, that are derived from pooled blood products. In the early stage of the HIV epidemic, a number of people became infected with the virus through blood transfusions, and nearly 90% of boys and men with hemophilia A contracted the virus. Blood clotting factors, such as Factor VIII, are now made via recombinant genetic technology, and no longer rely on blood products from donors, eliminating the risk of HIV spread. In the developed world, the blood supply is checked thoroughly and the risk of HIV transmission in incredibly small.

    An infected mother can spread HIV to her developing fetus. Taking HIV medication to prevent transmission of the virus during pregnancy, delivery and after birth has greatly diminished the risk of spreading the infection in this manner. An infected mother can also pass along the virus in her breast milk.

    HIV can be spread through organ donation, from an infected donor to an uninfected recipient. Organ donors and organs now undergo extensive testing to avoid this unfortunate situation.

    If you are concerned that you may have been exposed to HIV, a simple blood test can determine if you have been infected. The standard HIV blood test is designed to detect antibodies to the HIV virus in your blood. At least 95% of people will develop antibodies to HIV within six months of infection. A test performed too soon after infection may give a false-negative result.

    The most commonly used blood test is called an ELISA (enzyme-linked immunosorbent assay). The test is very sensitive, but occasionally it will give a false-positive result. Whenever an ELISA test comes back positive, a second more specific test known as a Western blot is performed to confirm the results. Both ELISA and Western blot tests require that you give blood during a first visit, and then return to get the results from your doctor one to two weeks later.

    Rapid screening tests have also been developed that provide results in 15 to 30 minutes, and require only a single office visit. A drawback to rapid testing, however, is that positive results will not be confirmed with a Western blot. Consequently, the rate of false positives is higher for rapid screening tests than for standard (ELISA plus Western blot) testing.

    Home collection kits for HIV testing are also available. There are many different tests available; however, only the Home Access Express HIV-1 Test System (a product of the Home Access Health Corporation) has been approved by the FDA. To perform this test, a person pricks a finger and blots the blood onto a piece of paper. The sample is then mailed to a lab, and the results are provided over the phone several days later. In clinical studies, this test was able to identify 100% of known positive samples, and 99.5% of HIV-1 negative samples.

    If your blood test is positive, your doctor will take a medial history to help determine the health of your immune system. When you first seek treatment for HIV, your doctor will take a medical history to identify factors that may affect the progression of your disease. The medical history will help your doctor to determine the overall health of your immune system, and thus will inform important treatment decisions. The average time for untreated HIV disease to progress from infection to development of AIDS is 10 to 11 years, so if you were infected soon before your positive test, you are unlikely to develop symptoms in the near future.

    You doctor will ask you questions to identify:

    • Symptoms related to HIV infection

    • Current medications you are taking and any allergies to medications

    • Past history of tuberculosis, hepatitis, or sexually transmitted diseases

    • Previous treatment with antiretroviral drugs

    • Previous immunizations

    • History of substance abuse

    Your doctor will perform a comprehensive physical examination. The most common symptoms of HIV infection your doctor will look for include weight loss, a white coating on your tongue that indicates a yeast infection (candidiasis or thrush), and signs of other infections that wouldn't normally occur in people with healthy immune systems.

    Your doctor will order additional blood tests to determine the health of your immune system and estimate the stage of your HIV infection. One test is designed to determine the number of CD4 cells in the blood, and the second is a test for HIV viral load. These tests help to stage the infection, determine when to begin or change antiretroviral therapy, and to monitor how well a particular drug or drug combination is working. The lower the viral load, the lower the risk of disease progression.

    Both CD4 counts and viral load testing will generally be done every three to four months after diagnosis to monitor the progression of the disease.

    The risk of contracting HIV can be reduced through sexual abstinence or by engaging in safer sexual practices. HIV is most commonly transmitted through exchange of bodily fluids during intercourse or other types of sexual behaviors. Abstinence is the only way to completely eliminate the risk of contracting HIV through sexual encounters. Engaging in safer sexual practices, however, is a more realistic way for people to reduce their risk of contracting HIV.

    Latex and polyurethane condoms provide an impenetrable barrier to HIV, and when used with every sexual encounter, provide effective prevention against infection. Condoms should only be used before their expiration date, and when no obvious signs of defects or damage are visible.

    The U.S. government's Centers for Disease Control and Prevention recommend the following:

    • Use a new condom with each act of intercourse.

    • Carefully handle the condom to avoid damaging it with fingernails, teeth, or other sharp objects.

    • Put the condom on after the penis is erect and before any genital contact with your partner.

    • Ensure that no air is trapped in the tip of the condom.

    • Ensure adequate lubrication during intercourse, possibly requiring use of lubricants such as KY Jelly or glycerine. Never use oil-based lubricant such as petroleum jelly, shortening, mineral oil, massage oils, body lotions, or cooking oil. Oil can weaken latex, leading to tears in the condom.

    • Hold the condom firmly against the base of the penis during withdrawal. Withdraw while the penis is still erect to prevent slippage.

    Having a monogamous sexual relationship with an uninfected partner can dramatically reduce your risk of contracting HIV. The primary risk in these cases, however, is that one or both of the partners may not be completely truthful about having sex outside the relationship with people who could be infected with HIV.

    Partners considering a monogamous relationship can be tested to confirm their HIV status, but they should remember that the HIV antibody test may miss infections that occurred six months or less before the test was performed.

    Avoiding high-risk sexual practices such as anal intercourse can reduce the risk of HIV transmission. Unprotected anal intercourse is considered to carry the highest sexual risk of HIV transmission. Microscopic cuts or abrasions that occur in both partners during anal intercourse allow the virus to get directly into the bloodstream. Unprotected vaginal intercourse is also considered to carry a relatively high risk of HIV transmission.

    Use safer-sex precautions if you engage in oral sex. While it was commonly thought that unprotected oral sex posed a lower risk for HIV transmission than did unprotected vaginal or anal intercourse, a recent study of 122 people with a primary HIV infection revealed that 6% of that group had been infected through oral sex. This study refutes the previous notion of unprotected oral sex as “safe,” and underscores the importance of consistently engaging in safer sex practices.

    Intravenous drug users can reduce their risk of contracting HIV by not reusing or sharing needles. Half of all new HIV infections in the U.S. are estimated to occur among people who inject illegal drugs. Because many of these infections could be prevented if drug users did not use contaminated needles or syringes, needle exchange programs have been set up in more than 80 cities in 38 states in the U.S. The details vary, but the programs generally distribute clean needles and syringes, safely dispose of used ones, and offer referrals for drug treatment and counseling.

    The risk of passing HIV from a mother to her child during pregnancy or birth can be reduced through drug treatment Table 03. In 1994, a pivotal clinical trial demonstrated that a three-part drug regimen of zidovudine (AZT) could reduce the risk of HIV transmission from the mother to her child by 70%.

    Since 1994, however, several new drugs have been developed. Current treatment recommendations for adults and adolescents include using combination therapy, which has proved to be more effective than AZT alone. While this new combination therapy would be most effective for treating a pregnant woman, its effectiveness for preventing transmission to the child remain unclear. Taking these factors into account, The U.S. Public Health Service Task Force currently recommends that physicians offering combination therapy as an option to HIV-infected pregnant women fully inform them of its potential benefits and risks. The Task Force further recommends that pregnant women consider delaying therapy until 10 to 12 weeks into pregnancy, because early pregnancy is the period in which the fetus is most susceptible to drug-induced birth defects.

    Table 3.  Prevention of HIV Transmission from Mother to Child

    Time of administration Regimen
    Before birth Oral administration of zidovudine (AZT) to the mother twice daily, started at 14 to 34 weeks of pregnancy and continued until birth.
    At birth Intravenous administration of zidovudine to the mother, begun during labor and continued until delivery.
    After birth Oral administration of zidovudine to the newborn for the first six weeks of life, beginning at 8 to 12 hours after birth.

    Adapted from the U.S. Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant Women Infected with HIV-1 for Maternal Health and for Reducing Perinatal HIV-1 Transmission in the United States, Feb. 25, 2000.

    Using formula rather than breast milk can reduce the risk that an infant will contract HIV from breast milk. HIV can be passed from a mother to her child through breast milk. As many as 40% of pediatric HIV infections in developing countries are thought to be caused by breast milk, the risk increasing the longer the child is breastfed. In the U.S. and other industrialized countries, national health authorities recommend that HIV-positive women not breastfeed their infants to reduce the risk of virus transmission.

    AZT treatment directly after a known exposure may stop HIV infection from developing. Healthcare workers exposed to HIV-contaminated blood through needlesticks have long been treated with AZT to prevent an HIV infection from becoming established. This treatment is known as postexposure prophylaxis, or PEP.  Most forms involve using one or more drugs within 72 hours of a possible exposure, continuing for a period of 4 weeks.

    Preliminary evidence shows that PEP is also effective after sexual or drug-related exposure to HIV. In a recent San Francisco study, 400 participants were given PEP after known HIV exposures. None of those treated had developed an HIV infection after 6 months.

  • Prevention and Screening

    The risk of contracting HIV can be reduced through sexual abstinence or by engaging in safer sexual practices. HIV is most commonly transmitted through exchange of bodily fluids during intercourse or other types of sexual behaviors. Abstinence is the only way to completely eliminate the risk of contracting HIV through sexual encounters. Engaging in safer sexual practices, however, is a more realistic way for people to reduce their risk of contracting HIV.

    Latex and polyurethane condoms provide an impenetrable barrier to HIV, and when used with every sexual encounter, provide effective prevention against infection. Condoms should only be used before their expiration date, and when no obvious signs of defects or damage are visible.

    The U.S. government's Centers for Disease Control and Prevention recommend the following:

    • Use a new condom with each act of intercourse.

    • Carefully handle the condom to avoid damaging it with fingernails, teeth, or other sharp objects.

    • Put the condom on after the penis is erect and before any genital contact with your partner.

    • Ensure that no air is trapped in the tip of the condom.

    • Ensure adequate lubrication during intercourse, possibly requiring use of lubricants such as KY Jelly or glycerine. Never use oil-based lubricant such as petroleum jelly, shortening, mineral oil, massage oils, body lotions, or cooking oil. Oil can weaken latex, leading to tears in the condom.

    • Hold the condom firmly against the base of the penis during withdrawal. Withdraw while the penis is still erect to prevent slippage.

    Having a monogamous sexual relationship with an uninfected partner can dramatically reduce your risk of contracting HIV. The primary risk in these cases, however, is that one or both of the partners may not be completely truthful about having sex outside the relationship with people who could be infected with HIV.

    Partners considering a monogamous relationship can be tested to confirm their HIV status, but they should remember that the HIV antibody test may miss infections that occurred six months or less before the test was performed.

    Avoiding high-risk sexual practices such as anal intercourse can reduce the risk of HIV transmission. Unprotected anal intercourse is considered to carry the highest sexual risk of HIV transmission. Microscopic cuts or abrasions that occur in both partners during anal intercourse allow the virus to get directly into the bloodstream. Unprotected vaginal intercourse is also considered to carry a relatively high risk of HIV transmission.

    Use safer-sex precautions if you engage in oral sex. While it was commonly thought that unprotected oral sex posed a lower risk for HIV transmission than did unprotected vaginal or anal intercourse, a recent study of 122 people with a primary HIV infection revealed that 6% of that group had been infected through oral sex. This study refutes the previous notion of unprotected oral sex as “safe,” and underscores the importance of consistently engaging in safer sex practices.

    Intravenous drug users can reduce their risk of contracting HIV by not reusing or sharing needles. Half of all new HIV infections in the U.S. are estimated to occur among people who inject illegal drugs. Because many of these infections could be prevented if drug users did not use contaminated needles or syringes, needle exchange programs have been set up in more than 80 cities in 38 states in the U.S. The details vary, but the programs generally distribute clean needles and syringes, safely dispose of used ones, and offer referrals for drug treatment and counseling.

    The risk of passing HIV from a mother to her child during pregnancy or birth can be reduced through drug treatment Table 03. In 1994, a pivotal clinical trial demonstrated that a three-part drug regimen of zidovudine (AZT) could reduce the risk of HIV transmission from the mother to her child by 70%.

    Since 1994, however, several new drugs have been developed. Current treatment recommendations for adults and adolescents include using combination therapy, which has proved to be more effective than AZT alone. While this new combination therapy would be most effective for treating a pregnant woman, its effectiveness for preventing transmission to the child remain unclear. Taking these factors into account, The U.S. Public Health Service Task Force currently recommends that physicians offering combination therapy as an option to HIV-infected pregnant women fully inform them of its potential benefits and risks. The Task Force further recommends that pregnant women consider delaying therapy until 10 to 12 weeks into pregnancy, because early pregnancy is the period in which the fetus is most susceptible to drug-induced birth defects.

    Table 3.  Prevention of HIV Transmission from Mother to Child

    Time of administration Regimen
    Before birth Oral administration of zidovudine (AZT) to the mother twice daily, started at 14 to 34 weeks of pregnancy and continued until birth.
    At birth Intravenous administration of zidovudine to the mother, begun during labor and continued until delivery.
    After birth Oral administration of zidovudine to the newborn for the first six weeks of life, beginning at 8 to 12 hours after birth.

    Adapted from the U.S. Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant Women Infected with HIV-1 for Maternal Health and for Reducing Perinatal HIV-1 Transmission in the United States, Feb. 25, 2000.

    Using formula rather than breast milk can reduce the risk that an infant will contract HIV from breast milk. HIV can be passed from a mother to her child through breast milk. As many as 40% of pediatric HIV infections in developing countries are thought to be caused by breast milk, the risk increasing the longer the child is breastfed. In the U.S. and other industrialized countries, national health authorities recommend that HIV-positive women not breastfeed their infants to reduce the risk of virus transmission.

    AZT treatment directly after a known exposure may stop HIV infection from developing. Healthcare workers exposed to HIV-contaminated blood through needlesticks have long been treated with AZT to prevent an HIV infection from becoming established. This treatment is known as postexposure prophylaxis, or PEP.  Most forms involve using one or more drugs within 72 hours of a possible exposure, continuing for a period of 4 weeks.

    Preliminary evidence shows that PEP is also effective after sexual or drug-related exposure to HIV. In a recent San Francisco study, 400 participants were given PEP after known HIV exposures. None of those treated had developed an HIV infection after 6 months.

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Human Immunodeficiency Virus (HIV) Related Drugs

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