Understanding - HIV/AIDS

Understanding - HIV/AIDS

Human immunodeficiency virus (HIV) infection is an infection caused by one of the two viruses, HIV-1 and HIV-2. The HIV virus progressively destroy some type of white blood cells called lymphocytes. Lymphocytes are an important part of the body's immune defences. When lymphocytes are destroyed, the body becomes susceptible to attack by many other infections organisms. Many of the complication of HIV infection, including death, are usually the result of those infections and not of the HIV infection itself. Acquired immunodeficiency syndrome (AIDS) is the most severe form of HIV infection. A person with HIV infection is considered to have AIDS when at least one complicating illness develops or his ability to defeud against infection significantly declines as measured by a low CD4+ lymphocyte count.

Infections with HIV-1 and HIV-2 are serious and tend to occur in different regions. HIV-1 is most common in the Western Hemisphere, Europe, Asia and Central, South, and East Africa. HIV-2 is common in West Africa, although many people there are infected with HIV-1.

The HIV is a retrovirus, which like many other viruses stores its genetic information as RNA rather than as DNA. When the virus enters a targeted host cell, it releases its RNA and an enzyme (reverse transcriptase), and then makes DNA using the viral RNA as a pattern. The viral DNA is then incorporated into the host cell DNA. This reverses the pattern of human cells, which copy RNA from the pattern of human DNA (thus, the term 'retro' for 'backward'). Other RNA viruses, such as polio or measles, do not make DNA copies but supply their own RNA.

Each time a host cell divides, it makes as new copy of the integrated viral DNA along with its own genes. The viral DNA can either lie latent (hidden) and do no damage or activate to take over the functions of the cell, causing the cell to produce new viruses. These new viruses are released from the infected cell to invade other cells.

Transmission of Infection :
The transmission of HIV requires contract with a body fluid that contains the virus or infected cells. HIV can appear in nearly any body fluid, but transmission mainly comes from blood, semen, vaginal secretions, and breast milk. Although low concentrations of HIV are also present in tears, urine and saliva transmission from these fluids is extremely rare. HIV is transmitted in the following ways :

  1. Sexual contact with an infected person, during which the mucous membrane lining the mouth, vagina, penis, or rectum is exposed to contaminated body fluids (unprotected sex).
  2. Injection or infusion of contaminated blood, as occurs with blood transfusions, the sharing of needles, or an accidental prick from an HIV contaminated needle.
  3. Transfer of the virus from an infected mother to a child before birth, during, or after birth through the mother's milk.

Susceptibility to HIV infection increases when the skin or a mucous membrane is torn on damaged - even numerically - as can happen during vigorous vaginal or an intercourse. Sexual transmission of HIV is more likely if either partner has Syphilis, or another sexually transmitted disease (STD) like herpes, that produces breaks in the skin or inflammation of the genitals.

Mechanism of Infection :
Once in the body, HIV attaches to several types of white blood cells, the most important being the helper T lymphocyte. Helper T lymphocytes activate and co-ordinate other cells of the immune system. these lymphocytes have a receptor protein called CD4 in their outer membrane (and therefore, are called CDR+). HIV has its genetic material incoded in RNA. Once inside a 'CDR+' lymphocyte, the virus turns its RNA into DNA by means of on enzyme called reverse transcriptase. The viral DNA is incorporated into the DNA of the infected lymphocyte. The lymphocyte's own machinary then replicates (reproduces) the virus inside the cell eventually destroying the cell. The thousands of new viruses produced by each infected cell infect other lymphocytes and can destroy them all as well. Within a few days or weeks, enough HIV may be produced to reduce numbers of lymphocytes substantially and enable the person to spread the HIV infection to others.

Because HIV infection destroys CD4+ lymbhocytes, it weakens the body's system for protecting itself against certain infections and cancers. This weakening of the immune system is the cause of inability of the body to eliminate HIV infection once it has started.

Because the number of CD4+ lymphocytes in the blood helps determine the ability of the immune system to protect the body from infections it is a good measure of the severity of the damage done by HIV infection. A healthy person has a CD4+ lymphocyte count of roughly 800 to 1300 cells per microletre of blood. Typically 40 to 60 per cent of CD4+ lymphocytes are destroyed in the first few months of infection. After about six months, the CD4+ count stops falling so quickly, but it continues to decline. 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, the fungal infection that causes Pneumocystis carini pneumonia). A count below 50 cells per microliter of blood is particularly dangerous, because additional opportunistic infections that can rapidly cause severe weight loss, blindness, or death commonly occurs.

Symptoms :
Most people experience no noticeable symptoms upon initial infection. However within a few weeks of HIV infection, fever, rashes, swollen lymph nodes, fatigue and a variety of less common symptoms may develop and may last a few weeks. The symptoms disappear, although the lymph nodes may stay enlarged. An infected person is able to spread the virus soon after becoming infected. This is true even if there are no symptoms. A person can have HIV infection for years - even a decade or longer - before developing AIDS. However before AIDS develops, some may develop a variety of non-specific symptoms such as swollen lymph nodes, weight loss, fatigue, recurrent fever or diarrhoea, anaemia, and thrush (oral fungal infection). In some people, HIV is probably directly responsible for AIDS wasting. This wasting may also be caused by a series of infections or an untreated infection (such as tuberculosis) in people with AIDS.

Kapasi’s sarcoma, a cancer that appears as painless, red to purple, raised patches on the skin, affects many people with AIDS, especially homosexual men. Cancers of the immune system (lymphomas, typically non-hodgekin lymphona) may develop. Women are proved to develop cancer cervix. Homosexual men are prone to developing cancer of the rectum. Usually death is caused by the cumulative effects of wasting, dementia, opportunistic infections, or cancers.

A relatively simple, accurate blood test that detects antibodies to HIV (ELISA test) is used, to screen people for HIV infection. If the ELISA result is positive, it is confirmed with a more accurate test, usually the Western Blot. Both tests often are not positive in the first month or two after HIV infection because it takes the body that long to produce antibodies against the virus. Other tests (for example, viral load tests or P24 antigen) detect HIV in the blood much sooner after infection. P24 antigen is currently used along with other tests to screen blood donated for transfusions.

People diagnosed with HIV infection have their blood tested regularly to measure the CD4+ count and viral load. CD4+ counts indicate the health of a person's immune system and, when low, their chances of becoming ill from an infection. Viral load is a predictor of how fast the CD4+ count is likely to drop over the next year. Doctors use these two measurements to decide when to start drugs for both

Three classes of drugs are available to treat HIV infection: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transrcriptase inhibitors, and protease inhibitors. Both types of reverse transcriptase inhibitors work by interfering with the HIV enzyme re-verse trartscriptase, which converts viral RNA into DNA. Protease inhibitors interfere with the HIV enzyme protease, which is needed to activate certain proteins inside newly produced viruses. Failure to activate these pro-teins results in immature, defective HIV that does not infect new cells. None of these drugs kill HIV; they prevent the virus from replicating. If replication is sufficiently slowed, the destruction of CD4 cells by HIV is decreased dramatically and CD4+ counts begin to rise. The result can be reversal of much of the damage to the immune system caused by HIV.

HIV usually develops resistance to any of these drugs when they are used alone. Resistance can develop after a few days to several months of use, depending on the drug and the person. Therefore, treatment is most effective when at least two or three of the drugs are given in combination-usually one or two reverse transcriptase inhibitors plus a protease inhibitor. This combination of drugs is sometimes referred to as a drug cocktail." Combinations of drugs are used for three reasons. First, combinations are more powerful than single drugs in reducing levels of HIV in the blood. Second, combinations help prevent the development of drug resistance. Third, some HIV drugs (like ritrovirals) boost the blood levels of other HIV drugs (including most protease inhibitors) by slowing their removal from the body. Drug combinations have delayed the onset of AIDS in HIV-infected people, thus extending their lives.

Drug treatment is beneficial only when the drugs are taken on schedule, Missed doses allow the virus to replicate and develop resistance. The goal of combination therapy is to reduce the viral load so it is below detectable levels.

No treatments have proven able to eliminate the virus from the body, although levels often fall below what can he measured; if treatment is stopped, viral load increases and CD4+ counts begin to fall.

It is not yet clear for which infected people drug treatment should be started, but people with low CD4+ counts or high viral loads require treatment, even if they have no symptoms. Because of the many significant and unpleasant side effects and because the drugs are very expensive, it is not easy for people with HIV infection to take the drugs for many years without fail. Because taking HIV drugs irregularly often leads to drug resistance, doctors try to ensure that anyone prescribed these drugs is both willing and able to adhere to the treatment schedule.

People with low CD4+ counts are routinely prescribed drugs to prevent opportunistic infections. To prevent Pneumocystis pneumonia, the combination of sulfamethoxazole and trimethoprim is given when the CD4+ count drops below 200 cells per microliter of blood. This combination of drugs also prevents toxoplasmosis, which can damage the brain of a person with AIDS. For people with CD4+ counts below 50 cells per microliter of blood, azithromycin taken weekly or clarithromycin or rifabutin taken daily may prevent Mycobacterium avium infections. People recovering from cryptococcal meningitis or those experiencing repeated infections of the mouth, esophagus, or vagina with the fungus Candida may be given the antifungal drug flucanazole for prolonged periods. People with recurring episodes of herpes simplex infections of the mouth, lips, genitals, or rectum may require prolonged treatment with an antiviral drug (such as acyclovir) to prevent relapses.

Other drugs may help with the weakness and weight loss associated with AIDS. Megestrol and dronabinol (a marijuana derivative) stimulate appetite. Many people with AIDS claim that natural marijuana is even more effective, and use of marijuana for this purpose has been legalised in a few states. Anabolic steroids (such as testosterone) can also significantly reverse the loss of muscle tissue. Testosterone levels are reduced in some men and can be replaced by use of injections or patches on the skin.

Exposure to HIV does not always lead to infection, and some people who have had repeated exposures over many years remain uninfected. Moreover, many infected people have remained well for more than a decade. Doctors do not fully understand why some people become ill so much sooner than others, but a number of genetic factors appear to influence both susceptibility to infection and progression to AIDS after infection. Of the people infected with HIV who do not receive drug treatment, each year 1 to 2 per cent develop AIDS for the first several years after infection. Every year thereafter, about 5 per cent of the people with untreated HIV infection develop AIDS.

Submitted By
Dr Maswoodur Rahman Prince

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