Human Immunodeficiency Virus Infection and Global HIV/AIDS Status

Human immunodeficiency virus (HIV) infection is an infection by one of two viruses, HIV-1 and HIV-2. The HIV viruses progressively destroy some types of white blood cells called lymphocytes. Lymphocytes are an important part of the body's immune defenses. When lymphocytes are destroyed, the body becomes susceptible to attack by many other infectious organisms. Many of the complications of HIV infection, including death, are usually the result of these other infections and not of the HIV infection itself.

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.

Transmission of Infection

The transmission of HIV requires contact 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:

Susceptibility to HIV infection increases when the skin or a mucous membrane is torn or damaged-even minimally-as can happen during vigorous vaginal or anal intercourse. Sexual transmission of HIV is more likely it either partner has herpes, syphilis, or another sexually transmitted disease (STD) that produces breaks in the skin or inflammation of the genitals. However, HIV can be transmitted even if neither partner has other STDs or obvi-ous breaks in the skin. HIV transmission also can occur during oral sex, although it is far less common than during vaginal or anal intercourse.

HIV infection in a large number of women of childbearing age has led to HIV infection in children. In about 25 to 35 per cent of the pregnancies involving women infected with HIV, the virus is transmitted to the fetus through the placenta or, more commonly, at birth during passage through the birth canal. Infants who are breastfed can contract HIV infection through breast milk. A few children contract HIV infection through sexual abuse.

HIV is not transmitted by casual contact or even by close, nonsexual contact at work, school, or home. No case of HIV transmission has been traced to the coughing or sneezing of an infected person or to a mosquito bite. Transmission from an infected doctor or dentist to a patient is extremely rare.

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 coordinate other cells of the immune system. These lymphocytes have a receptor protein called CD4 in their outer membrane (and are therefore designated as CD4+). HIV has its genetic material encoded in RNA. Once inside a CD4+ lymphocyte, the virus turns its RNA into DNA by means of an enzyme called reverse transcriptase. The viral DNA is incorporated into the DNA of the infected lymphocyte. The lymphocyte's own machinery then reproduces (replicates) 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 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+ lymphocytes, it weakens the body's system for protecting itself against certain infections and cancers. This weakening of the immune system 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 of infection, the body produces lymphocytes and antibodies that help to lower the amount of HIV in the blood and keep the infection under control. For this reason, HIV infection can continue for a long time in some people before it causes serious problems.

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 1,300 cells per microliter of blood. Typically, 40 to 60 per cent of CD4+ lymphocytes are destroyed in the first few months of infection. After about 6 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 sys-tem becomes less able to fight certain infections /for example, the fungal infection that causes Pneumocystis carinii pneumonia [PCP]). These infections do not usually appear in people with a healthy immune system and are called opportunistic infections. 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.

The amount of virus in the blood is called the viral load. In the first few months after infection, a large number of virus particles circulate in the blood. The infection is very contagious at this stage. Later, the viral load drops to a lower level that remains constant for some time. This level is an important indicator of how contagious a person's infection is and how fast the disease is likely to progress. Doctors measure the viral load during treatment, because a decreasing or very low level indicates that treatment is working. The goal of treatment is to lower the viral load to the point where it is undetectable (suppressed) in the blood, although some virus is probably still present. A rise in the viral load may indicate the development of drug resistance or failure to take the drugs.

Symptoms

Most people experience no noticeable symptoms upon initial infection. However, fever, rashes, swollen lymph nodes, fatigue, and a variety of less common symptoms may develop within a few weeks of HIV infection and 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. Before AIDS develops, many people feel well, although some develop a variety of non-specific symptoms. These symptoms include swollen lymph nodes, weight loss, fatigue, recurring fever or diarrhea, anemia, and thrush (a fungal infection of the mouth).

The main symptoms of AIDS are those of the specific opportunistic infections and cancers that develop. HIV can also directly infect the brain, causing memory loss, weakness, difficulty walking, and difficulty in thinking and concentrating (dementia). In some people, HIV is probably directly responsible for AIDS wasting, which is a significant loss of weight with or without an obvious cause. Wasting in people with AIDS may also be caused by a series of infections or an untreated infection (such as tuberculosis) that persists. Kidney failure, which may be a direct effect of HIV, is more common in blacks than in whites.

Kaposi'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-Hodgkin's lymphoma) may develop, sometimes first appearing in the brain, where they can cause confusion, personality changes, and memory loss. Women are prone to developing cancer of the 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.

Diagnosis

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 the treatment of HIV and the prevention of the complicating infections. Doctors also use these tests to monitor the effects of treatment. With successful treatment, the viral load falls to low levels within weeks and the CD4+ count begins a long, slow recovery toward normal levels. AIDS is diagnosed when the CD4+ count falls below 200 cells per microliter of blood, there is extreme wasting, or certain opportunistic infections and cancers develop.

Prevention

Because HIV is nearly always transmitted by sexual contact or the sharing of needles, infection is almost completely preventable. Unfortunately, the measures required for prevention-sexual abstinence or condom use® and access to clean needles-are sometimes personally or socially unpopular. Many people have difficulty changing their addictive or sexual behaviors, so they continue to engage in behavior that puts them at risk for HIV infection. Additionally, safe sex practices are not foolproof: condoms can leak or break.

Vaccines for preventing HIV infection or slowing the progression of AIDS in people who are already infected have so far proved elusive. Research continues, and several promising vaccines are being tested.

Because HIV is not transmitted through the air or by casual contact (such as touching, holding, or dry kissing), hospitals and clinics do not isolate HIV-infected people unless they have another contagious infection. HIV-contaminated surfaces can easily be cleaned and disinfected because HIV is inactivated by heat and by common disinfectants such as hydrogen peroxide and alcohol. People who are , likely to come into contact with blood or other body fluids at their job should wear prortective gear, including latex gloves, masks, and eye shields. These universal precautions apply to body fluids from all people, not just '' those from someone with HIV, for two reasons! people with HIV may not know that they are infected, and other viruses can be transmitted by body fluids.

People who have been exposed to HIV from a blood splash, needlesticlc, or sexual contact may reduce the chance of infection by taking a brief course of anti-HIV drugs. These drugs must be started as soon as possible after the exposure. Four weeks of preventive treatment with two or three drugs is currently recommended. Because the risk of infection varies, doctors and infected people make treatment

Strategies for Preventing the Transmission of HIV

Treatment

Three classes of drugs are available to treat HIV infection: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Both types of reverse transcriptase inhibitors work by interfering with the HIV enzyme re-verse transcriptase, 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 proteins 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 dam-age 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 re-verse transcriptase inhibitors plus a protease inhibitor. This combination of drugs is some-times 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 ritonavir) 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.

Combinations of HIV drugs have both unpleasant and serious side effects. Disturbances in the metabolism of fats appear to be caused primarily by the protease inhibitors. Symptoms are the slow migration of body fat from the face, arms, and legs to the abdomen ("pro-tease paunch") and sometimes to the breasts of women. Blood levels of cholesterol and triglycerides, two forms of fat in the blood, are increased-probably increasing the risk of future heart attacks and strokes.

Nucleoside reverse transcriptase inhibitors damage mitochondria, a critical site of energy generation in human cells. Their side effects include anemia, painful feet caused by nerve damage, and liver damage that rarely progresses to liver failure. Individual drugs differ in their tendency to cause these problems. Careful monitoring and changes of drugs can usually prevent serious problems.

Prognosis

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. Within 10 to 11 years of contracting HIV infection, half of the people who have not received treatment develop AIDS. Eventually, more than 95 per cent of untreated infected people develop AIDS, and it is possible that they all will if they live long enough, although a few people have remained well for more than 15 years.

Early in the AIDS epidemic, many people with AIDS experienced a rapid decline in their quality of life after first being hospitalized for the infection-often spending much of their remaining time in the hospital. Most people died within 2 years of developing AIDS. However, current therapy has changed AIDS into a more stable, manageable disease. Many people have lived for years with AIDS, continuing to lead productive and active lives. Nevertheless, illness from infections and the expense and side effects of drugs may reduce quality of life. For people unable to tolerate or take drugs consistently, the natural progression of the disease resumes. Cure is not yet possible, although intensive research on a cure continues.

Submitted By:
DR MASWOODUR RAHMAN PRINCE

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