infections
Human Immunodeficiency Virus (HIV) Infection
Mechanism of HIV Infection
Once in the body, HIV attaches to several types of white blood cells. The most important are certain helper T lymphocytes ( T cells ). Helper T lymphocytes activate and coordinate other cells of the immune system. On their surface, these lymphocytes have a receptor called CD4, which enables HIV to attach to them. Thus, these helper lymphocytes are designated as CD4 HIV is a What Is a Retrovirus? . That is, it stores its genetic information as ribonucleic acid ( The HIV DNA copy is incorporated into the DNA of the infected lymphocyte. The lymphocyte’s own genetic machinery then reproduces (replicates) the HIV. Eventually, the lymphocyte is destroyed. Each infected lymphocyte produces thousands of new viruses, which infect other lymphocytes and destroy them as well. Within a few days or weeks, the blood and genital fluids contain a very large amount of HIV, and the number of CD4+ lymphocytes may be reduced substantially. Because the amount of HIV in blood and genital fluids is so large so soon after HIV infection, newly infected people transmit HIV to other people very easily. Like all viruses, human immunodeficiency virus (HIV) reproduces (replicates) using the genetic machinery of the cell it infects, usually a CD4+ lymphocyte. HIV first attaches to and penetrates its target cell. HIV releases RNA, the genetic code of the virus, into the cell. For the virus to replicate, its RNA must be converted to DNA. The RNA is converted by an enzyme called reverse transcriptase (produced by HIV). HIV mutates easily at this point because reverse transcriptase is prone to errors during the conversion of viral RNA to DNA. The viral DNA enters the cell’s nucleus. With the help of an enzyme called integrase (also produced by HIV), the viral DNA becomes integrated with the cell’s DNA. The DNA of the infected cell now produces viral RNA as well as proteins that are needed to assemble a new HIV. A new virus is assembled from RNA and short pieces of protein. The virus pushes (buds) through the membrane of the cell, wrapping itself in a fragment of the cell membrane and pinching off from the infected cell. To be able to infect other cells, the budded virus must mature. It becomes mature when another HIV enzyme (HIV protease) cuts structural proteins in the virus, causing them to rearrange. Medications used to treat HIV infection were developed based on the life cycle of HIV. These medications inhibit the three enzymes (reverse transcriptase, integrase, and protease) that the virus uses to replicate or to attach to and enter cells. When HIV infection destroys CD4+ lymphocytes, it weakens the body’s immune system, which protects against many infections and cancers. This weakening is part of the reason that the body is unable to eliminate HIV infection once it has started. However, the immune system is able to mount some response. Within a month or two after infection, the body produces lymphocytes and antibodies that help lower the amount of HIV in the blood and keep the infection under control. For this reason, untreated HIV infection may cause no symptoms or only a few mild symptoms for an average of about 10 years (ranging from 2 to more than 15 years). HIV also infects other cells, such as cells in the skin, brain, genital tract, heart, and kidneys, causing disease in those organs. The number of CD4+ lymphocytes in blood (the CD4 count) helps determine the following: How well the immune system can protect the body from infections How severe the damage done by the HIV is Most healthy people have a CD4 count of 500 to 1,000 cells per microliter of blood. Typically, the number of CD4+ lymphocytes is reduced during the first few months of infection. After about 3 to 6 months, the CD4 count stabilizes, but without treatment, it usually continues to decline at rates that vary from slow to rapid. If the CD4 count falls below about 200 cells per microliter of blood, the immune system becomes less able to fight certain infections (such as Overview of Pneumonia ). Most of these infections are rare in healthy people. However, they are common among people with a weakened immune system. Such infections are called opportunistic infections because they take advantage of a weakened immune system. A count below about 50 cells per microliter of blood is particularly dangerous because additional opportunistic infections that can rapidly cause severe weight loss, blindness, or death commonly occur. These infections include Cytomegalovirus (CMV) Infection None Mycobacterium avium Complex (MAC) Infections None The amount of HIV in the blood (specifically the number of copies of HIV RNA) is called the viral load. Viral load represents how quickly HIV is replicating. When people are first infected, the viral load increases rapidly. Then, after about 6 months, even without treatment, it drops to a lower level, which remains constant, called the set point. This level varies widely from person to person—from as little as a few hundred to over a million copies per microliter of blood. Viral load also indicates How contagious the infection is How fast the CD4 count is likely to decrease How fast symptoms are likely to appear The higher the set point of the viral load, the more quickly the CD4 count decreases to the low levels (less than 200) that increase risk of opportunistic infections, even in people without symptoms. During successful treatment, the viral load decreases to very low or undetectable levels (less than about 20 to 40 copies per microliter of blood). However, inactive (latent) HIV is still present within cells, and if treatment is stopped, HIV starts replicating and the viral load increases. An increase in the viral load during treatment may indicate the following: The HIV has developed resistance to antiretroviral treatment. The person is not taking the prescribed medications. Both Some people are infected with HIV for years before they develop symptoms. 