Disease: Human Immunodeficiency Virus (HIV)

    Human immunodeficiency virus (HIV) facts

    • HIV is the virus that causes HIV infection and the acquired immunodeficiency syndrome (AIDS).
    • Anal or vaginal sexual intercourse and illicit injectable drug use commonly transmit HIV. Infected mothers may also transmit HIV to their child during pregnancy or breastfeeding. Less common routes of transmission include needle-stick injuries or exposure to contaminated blood.
    • The blood supply in the United States is tested for HIV before use, and statistics show the risk of acquiring HIV infection from a transfusion is less than one in 1.5 million.
    • HIV attacks the immune system, especially cells known as CD-4 lymphocytes. Serious impairment of the CD-4 lymphocytes makes people susceptible to specific infections and cancers.
    • Untreated HIV infected progresses through three stages, with stage three being AIDS.
    • Health-care professionals diagnose HIV with tests that measure antibodies against the virus or measure the virus directly.
    • Treatment with highly active antiretroviral therapy (HAART or ART) dramatically increases life expectancy although it does not cure HIV infection.

    What is the human immunodeficiency virus?

    The human immunodeficiency virus is the cause of HIV infection and the acquired immunodeficiency syndrome (AIDS). HIV belongs to a family of organisms known as retroviruses. Once someone acquires the virus, it attaches to and enters human cells, especially cells known as CD4 T-cells, macrophages, and dendritic cells. The virus contains RNA, which it transcribes into DNA using an enzyme called reverse transcriptase. The resulting DNA integrates into the human genome in the cell. In this way, the virus fools the human genome into making more copies of the virus.

    HIV may remain quiescent (latent) in the genome or may be actively transcribed, causing the virus to replicate. HIV is a prolific virus and is able to create trillions of copies of itself in a short period of time. During times of peak viral reproduction, even 1 milliliter of blood can contain more than 1 million copies of the virus. Many of these copies differ in small ways from the original virus and may be resistant to different medications. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is the primary cause of HIV infection and AIDS in the world. HIV-2 is less common and less easily transmitted.

    What is the history of HIV?

    Although HIV infection is only a recent discovery, scientists have shown that HIV-1 may have spread to humans over 100 years ago. The likely source was primate-to-human transmission through bites or blood exposure, with chimpanzees being the most likely candidate for HIV-1 transmission to humans.

    Isolated human cases existed long before HIV infection came to the attention of the physicians. It is not entirely clear what caused HIV to begin to spread more widely in the mid-20th century. HIV was identified in tissue preserved from patients who died as early as 1959. In the late 1960s or early 1970s, it is thought that HIV infection spread to Haiti and then to the United States. Entering the homosexual male community predominately, the virus began to spread among people with multiple sexual partners. Over time, often a decade after infection, people with HIV infection began to get unusual infections, develop AIDS, and die.

    In 1981, the Centers for Disease Control and Prevention first took note of a cluster of pneumonia causes by Pneumocystis jirovecii (formerly known as Pneumocystis carinii), which was a highly unusual pathogen to find in young men. Affected individuals were noted to have depleted counts of a specific type of immune cell, known as the CD-4 T cell. Subsequent investigation revealed that homosexual men with multiple partners were most likely to have disease, suggesting that sexual activity was a key factor in transmission. Soon, scientists discovered the disease in people injecting illicit drugs, in heterosexuals with multiple sexual partners, in people who received blood products, and in babies born to infected mothers. A global effort was undertaken to identify the virus, leading to the description of HIV as the likely cause of AIDS by Dr. Luc Montagnier in France and by Dr. Robert Gallo in the United States. A test for HIV was soon developed and used to diagnose individuals and to ensure the safety of the blood supply.

    What causes an HIV infection?

    HIV is transmitted when infected material such as blood or semen or other infected fluids gains access to a new host. In the United States, surveillance statistics show there are approximately 1.1 million people living with HIV infection, but 18% are unaware that they are infected. Approximately 50,000 people get infected with HIV each year. Although the epidemic first was recognized in homosexual men, it has spread broadly throughout the U.S. New infections affect people from all subpopulations, although some groups are more likely to be affected than others. Of the 47,500 new infections in 2010, 63% were in men who had sex with men (MSN), 25% were acquired through heterosexual contact, and 8% were from injection drug use. HIV infection has hit the African-American community harder than other groups, with 44% of new infections occurring in this population, compared to 31% in whites and 21% in Hispanics. Over 600,000 Americans have died of HIV infection since the epidemic began.

    Worldwide, there are approximately 34 million people living with HIV, and there are 2.5 million new cases each year. Since HIV infection was recognized, there have been 30 million deaths as a result of HIV infection.

    What are the different stages of an HIV 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

    What are risk factors for an HIV infection?

    The most common modes of transmission in the United States are via

    • anal or vaginal sexual intercourse
    • use of illicit, injectable drugs where needles/syringes/materials are contaminated through sharing them with an HIV-infected person.

    Thus, the main risk factors for HIV infection are having nonmonogamous sexual intercourse, having unprotected sex (not using condoms), or the use of injectable illicit drugs. Transmission through oral sex is less common but is still possible.

    There is also a risk of transmission from infected mother to unborn child during pregnancy or delivery. Appropriate use of anti-HIV medications can significantly reduce this risk (see below) and has dramatically reduced the incidence of HIV in newborns in the United States. There is also some risk in the perinatal period because breast milk may harbor HIV, and infected mothers in the United States are counseled not to breastfeed. In developing countries, alternatives to breast milk may be lacking and recommendations may differ. Currently, there are approximately 200 new HIV cases per year in the U.S. in children younger than 13 years of age, and most (75%) were infected after birth.

    Other less common modes of transmission include accidental needle stick or sharps injuries in health-care workers and splashes of contaminated material onto mucous membranes or nonintact skin. Risk factors include unsafe practices for handling used needles or sharps, inappropriate disposal of needles/sharps, and inadequate use of personal protective measures such as gloves, masks, and eye protection when there is a chance of splashing.

    The blood supply in the United States is tested for HIV before use and the risk of acquiring HIV infection from a transfusion is less than one in 1.5 million.

    Casual contact (shaking hands, sneezing, coughing, sharing drinking glasses, sharing a toilet, exposure to saliva from social kissing, etc.) does not pose a threat for HIV infection.

    What are HIV infection symptoms and signs?

    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.

    How do health-care professionals diagnose an HIV infection? What are the different types of HIV tests?

    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.

    What is the treatment for an HIV infection?

    Medicines have been developed to inhibit almost all stages of the viral lifecycle. These are called highly active antiretroviral therapy (ART) and include the following:

    • Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) inhibit the ability of the virus to turn RNA into DNA. These medicines work by blocking the effect of a viral enzyme called reverse transcriptase. The virus needs to make DNA in order to insert it into the human genome. The earliest example of an NRTI was zidovudine (Retrovir), also known as AZT. NRTIs resemble the building blocks of nucleic acids and fool the enzyme into using them, which terminates the DNA strand.
    • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) also block the reverse transcriptase enzyme, although in a slightly different way from NRTIs.
    • Protease inhibitors (PIs) inhibit a viral enzyme (protease) that the virus uses to turn long strands of protein into usable pieces. Viruses made in the presence of PIs are inactive and ineffective. A PI called ritonavir (Norvir) is used to increase (boost) the potency of other PIs.
    • Entry inhibitors were developed to keep viruses from entering cells.
    • Integrase inhibitors impair the ability of the transcribed viral DNA to insert into the human genome.

    With so many options, it may be surprising that none of these drugs or combinations of these drugs has been shown to cure HIV. The problem lies in the ability of the virus to mutate and become resistant to medications. In addition, copies of the viral DNA can lie quietly in the human genome secluded from the ability of the drugs to act. This creates a latent reservoir for resurgent infection.

    Treatment for individual patients depends on the sensitivity of their virus to medications, which can be measured though viral genotyping. Viral genotyping, a kind of drug resistance testing, determines if any anti-HIV medications will not be effective against a person's strain of HIV. Viral genotyping is recommended for all patients in the U.S.

    Treatment may need to be individualized to minimize side effects in patients with underlying medical conditions, such as diabetes or heart disease. Pregnant patients should be treated by clinicians who are experts in this area and will not be covered the current article. However, it is important to note that treatment of HIV during pregnancy can dramatically reduce the risk of transmission to the unborn child.

    Opinions on when to start ART have evolved over time. In 2013, the National Institutes of Health recommended that ART be given to all patients infected with HIV, regardless of the stage of infection. The goal of this recommendation was to reduce the risk of disease progression and to reduce the risk of contagion. Early treatment can also lead to reduction in HIV-associated inflammation and associated complications, which include cardiovascular and kidney disease. It is important to note that patients on treatment are not cured and can still spread the infection, but treatment reduces the amount of virus in contaminated fluids and therefore reduces the risk of spread.

    What are complications of an HIV infection?

    Complications of HIV infection most often stem from impairment of the immune system, especially CD-4 lymphocyte-mediated immunity. As HIV enters stage 3, the immune impairment predisposes patients to AIDS-defining conditions such as infections and cancers. With effective treatment, many patients will not progress to stage 3 infection. There is increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation. End-organ damage may occur at all stages of infection. Although ART is effective in prolonging life and reducing the risk of disease progression, all treatment regimens have side effects, which range from minor problems like fatigue to more serious problems like liver damage.

    What is the prognosis of an HIV infection?

    Without treatment, HIV infection progresses to AIDS in approximately 10 years, with death following within three years after onset of AIDS. With appropriate treatment, a 20-year-old with HIV infection can expect to live to reach 71 years of age. This dramatic increase in life expectancy emphasizes the need for early diagnosis and treatment. Moreover, with newer treatment regimens and guidelines, there is every reason to think that life expectancy will continue to increase in patients who are able to receive appropriate treatment. There are some factors that decrease life expectancy, including use of illicit drugs and the coexistence of other conditions like chronic hepatitis.

    Is it possible to prevent the transmission of HIV?

    It's possible to prevent HIV transmission by eliminating sexual intercourse with an infected person and avoiding exposure to potentially contaminated body fluids. Unfortunately, many people with HIV do not know they are infected and inadvertently spread the virus. Treatment can reduce the amount of virus in semen and secretions, but it does not completely eliminate the risk of HIV transmission. A good rule for dating is to assume that sexual partners are infected unless known to be otherwise. Using condoms with every sexual encounter reduces the risk of infection, although it does not eliminate the risk because condoms may break or leak. Needle-exchange programs have reduced the risk of new infection in populations that use illicit drugs. As discussed above, mother-to-child transmission can be dramatically reduced by treating the infected mother during pregnancy, treating the baby at birth, and avoiding breastfeeding. Items that may be contaminated with blood, such as razors or toothbrushes, should not be shared.

    Health-care workers who have had a needle stick or other exposure to HIV-contaminated blood should be evaluated to determine whether or not they should take medications as prophylaxis. The types of medicine and the duration of treatment are dependent on the degree of exposure.

    What is the history of HIV?

    Although HIV infection is only a recent discovery, scientists have shown that HIV-1 may have spread to humans over 100 years ago. The likely source was primate-to-human transmission through bites or blood exposure, with chimpanzees being the most likely candidate for HIV-1 transmission to humans.

    Isolated human cases existed long before HIV infection came to the attention of the physicians. It is not entirely clear what caused HIV to begin to spread more widely in the mid-20th century. HIV was identified in tissue preserved from patients who died as early as 1959. In the late 1960s or early 1970s, it is thought that HIV infection spread to Haiti and then to the United States. Entering the homosexual male community predominately, the virus began to spread among people with multiple sexual partners. Over time, often a decade after infection, people with HIV infection began to get unusual infections, develop AIDS, and die.

    In 1981, the Centers for Disease Control and Prevention first took note of a cluster of pneumonia causes by Pneumocystis jirovecii (formerly known as Pneumocystis carinii), which was a highly unusual pathogen to find in young men. Affected individuals were noted to have depleted counts of a specific type of immune cell, known as the CD-4 T cell. Subsequent investigation revealed that homosexual men with multiple partners were most likely to have disease, suggesting that sexual activity was a key factor in transmission. Soon, scientists discovered the disease in people injecting illicit drugs, in heterosexuals with multiple sexual partners, in people who received blood products, and in babies born to infected mothers. A global effort was undertaken to identify the virus, leading to the description of HIV as the likely cause of AIDS by Dr. Luc Montagnier in France and by Dr. Robert Gallo in the United States. A test for HIV was soon developed and used to diagnose individuals and to ensure the safety of the blood supply.

    What causes an HIV infection?

    HIV is transmitted when infected material such as blood or semen or other infected fluids gains access to a new host. In the United States, surveillance statistics show there are approximately 1.1 million people living with HIV infection, but 18% are unaware that they are infected. Approximately 50,000 people get infected with HIV each year. Although the epidemic first was recognized in homosexual men, it has spread broadly throughout the U.S. New infections affect people from all subpopulations, although some groups are more likely to be affected than others. Of the 47,500 new infections in 2010, 63% were in men who had sex with men (MSN), 25% were acquired through heterosexual contact, and 8% were from injection drug use. HIV infection has hit the African-American community harder than other groups, with 44% of new infections occurring in this population, compared to 31% in whites and 21% in Hispanics. Over 600,000 Americans have died of HIV infection since the epidemic began.

    Worldwide, there are approximately 34 million people living with HIV, and there are 2.5 million new cases each year. Since HIV infection was recognized, there have been 30 million deaths as a result of HIV infection.

    What are the different stages of an HIV 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

    What are risk factors for an HIV infection?

    The most common modes of transmission in the United States are via

    • anal or vaginal sexual intercourse
    • use of illicit, injectable drugs where needles/syringes/materials are contaminated through sharing them with an HIV-infected person.

    Thus, the main risk factors for HIV infection are having nonmonogamous sexual intercourse, having unprotected sex (not using condoms), or the use of injectable illicit drugs. Transmission through oral sex is less common but is still possible.

    There is also a risk of transmission from infected mother to unborn child during pregnancy or delivery. Appropriate use of anti-HIV medications can significantly reduce this risk (see below) and has dramatically reduced the incidence of HIV in newborns in the United States. There is also some risk in the perinatal period because breast milk may harbor HIV, and infected mothers in the United States are counseled not to breastfeed. In developing countries, alternatives to breast milk may be lacking and recommendations may differ. Currently, there are approximately 200 new HIV cases per year in the U.S. in children younger than 13 years of age, and most (75%) were infected after birth.

    Other less common modes of transmission include accidental needle stick or sharps injuries in health-care workers and splashes of contaminated material onto mucous membranes or nonintact skin. Risk factors include unsafe practices for handling used needles or sharps, inappropriate disposal of needles/sharps, and inadequate use of personal protective measures such as gloves, masks, and eye protection when there is a chance of splashing.

    The blood supply in the United States is tested for HIV before use and the risk of acquiring HIV infection from a transfusion is less than one in 1.5 million.

    Casual contact (shaking hands, sneezing, coughing, sharing drinking glasses, sharing a toilet, exposure to saliva from social kissing, etc.) does not pose a threat for HIV infection.

    What are HIV infection symptoms and signs?

    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.

    How do health-care professionals diagnose an HIV infection? What are the different types of HIV tests?

    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.

    What is the treatment for an HIV infection?

    Medicines have been developed to inhibit almost all stages of the viral lifecycle. These are called highly active antiretroviral therapy (ART) and include the following:

    • Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) inhibit the ability of the virus to turn RNA into DNA. These medicines work by blocking the effect of a viral enzyme called reverse transcriptase. The virus needs to make DNA in order to insert it into the human genome. The earliest example of an NRTI was zidovudine (Retrovir), also known as AZT. NRTIs resemble the building blocks of nucleic acids and fool the enzyme into using them, which terminates the DNA strand.
    • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) also block the reverse transcriptase enzyme, although in a slightly different way from NRTIs.
    • Protease inhibitors (PIs) inhibit a viral enzyme (protease) that the virus uses to turn long strands of protein into usable pieces. Viruses made in the presence of PIs are inactive and ineffective. A PI called ritonavir (Norvir) is used to increase (boost) the potency of other PIs.
    • Entry inhibitors were developed to keep viruses from entering cells.
    • Integrase inhibitors impair the ability of the transcribed viral DNA to insert into the human genome.

    With so many options, it may be surprising that none of these drugs or combinations of these drugs has been shown to cure HIV. The problem lies in the ability of the virus to mutate and become resistant to medications. In addition, copies of the viral DNA can lie quietly in the human genome secluded from the ability of the drugs to act. This creates a latent reservoir for resurgent infection.

    Treatment for individual patients depends on the sensitivity of their virus to medications, which can be measured though viral genotyping. Viral genotyping, a kind of drug resistance testing, determines if any anti-HIV medications will not be effective against a person's strain of HIV. Viral genotyping is recommended for all patients in the U.S.

    Treatment may need to be individualized to minimize side effects in patients with underlying medical conditions, such as diabetes or heart disease. Pregnant patients should be treated by clinicians who are experts in this area and will not be covered the current article. However, it is important to note that treatment of HIV during pregnancy can dramatically reduce the risk of transmission to the unborn child.

    Opinions on when to start ART have evolved over time. In 2013, the National Institutes of Health recommended that ART be given to all patients infected with HIV, regardless of the stage of infection. The goal of this recommendation was to reduce the risk of disease progression and to reduce the risk of contagion. Early treatment can also lead to reduction in HIV-associated inflammation and associated complications, which include cardiovascular and kidney disease. It is important to note that patients on treatment are not cured and can still spread the infection, but treatment reduces the amount of virus in contaminated fluids and therefore reduces the risk of spread.

    What are complications of an HIV infection?

    Complications of HIV infection most often stem from impairment of the immune system, especially CD-4 lymphocyte-mediated immunity. As HIV enters stage 3, the immune impairment predisposes patients to AIDS-defining conditions such as infections and cancers. With effective treatment, many patients will not progress to stage 3 infection. There is increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation. End-organ damage may occur at all stages of infection. Although ART is effective in prolonging life and reducing the risk of disease progression, all treatment regimens have side effects, which range from minor problems like fatigue to more serious problems like liver damage.

    What is the prognosis of an HIV infection?

    Without treatment, HIV infection progresses to AIDS in approximately 10 years, with death following within three years after onset of AIDS. With appropriate treatment, a 20-year-old with HIV infection can expect to live to reach 71 years of age. This dramatic increase in life expectancy emphasizes the need for early diagnosis and treatment. Moreover, with newer treatment regimens and guidelines, there is every reason to think that life expectancy will continue to increase in patients who are able to receive appropriate treatment. There are some factors that decrease life expectancy, including use of illicit drugs and the coexistence of other conditions like chronic hepatitis.

    Is it possible to prevent the transmission of HIV?

    It's possible to prevent HIV transmission by eliminating sexual intercourse with an infected person and avoiding exposure to potentially contaminated body fluids. Unfortunately, many people with HIV do not know they are infected and inadvertently spread the virus. Treatment can reduce the amount of virus in semen and secretions, but it does not completely eliminate the risk of HIV transmission. A good rule for dating is to assume that sexual partners are infected unless known to be otherwise. Using condoms with every sexual encounter reduces the risk of infection, although it does not eliminate the risk because condoms may break or leak. Needle-exchange programs have reduced the risk of new infection in populations that use illicit drugs. As discussed above, mother-to-child transmission can be dramatically reduced by treating the infected mother during pregnancy, treating the baby at birth, and avoiding breastfeeding. Items that may be contaminated with blood, such as razors or toothbrushes, should not be shared.

    Health-care workers who have had a needle stick or other exposure to HIV-contaminated blood should be evaluated to determine whether or not they should take medications as prophylaxis. The types of medicine and the duration of treatment are dependent on the degree of exposure.

    Source: http://www.rxlist.com

    The most common modes of transmission in the United States are via

    • anal or vaginal sexual intercourse
    • use of illicit, injectable drugs where needles/syringes/materials are contaminated through sharing them with an HIV-infected person.

    Thus, the main risk factors for HIV infection are having nonmonogamous sexual intercourse, having unprotected sex (not using condoms), or the use of injectable illicit drugs. Transmission through oral sex is less common but is still possible.

    There is also a risk of transmission from infected mother to unborn child during pregnancy or delivery. Appropriate use of anti-HIV medications can significantly reduce this risk (see below) and has dramatically reduced the incidence of HIV in newborns in the United States. There is also some risk in the perinatal period because breast milk may harbor HIV, and infected mothers in the United States are counseled not to breastfeed. In developing countries, alternatives to breast milk may be lacking and recommendations may differ. Currently, there are approximately 200 new HIV cases per year in the U.S. in children younger than 13 years of age, and most (75%) were infected after birth.

    Other less common modes of transmission include accidental needle stick or sharps injuries in health-care workers and splashes of contaminated material onto mucous membranes or nonintact skin. Risk factors include unsafe practices for handling used needles or sharps, inappropriate disposal of needles/sharps, and inadequate use of personal protective measures such as gloves, masks, and eye protection when there is a chance of splashing.

    The blood supply in the United States is tested for HIV before use and the risk of acquiring HIV infection from a transfusion is less than one in 1.5 million.

    Casual contact (shaking hands, sneezing, coughing, sharing drinking glasses, sharing a toilet, exposure to saliva from social kissing, etc.) does not pose a threat for HIV infection.

    Source: http://www.rxlist.com

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