The human immunodeficiency virus (HIV) weakens the body's immune defenses by destroying CD4 (T-cell) lymphocytes, which are a group of white blood cells that normally help guard the body against attacks by bacteria, viruses and other germs. When HIV destroys CD4 lymphocytes, the body becomes vulnerable to many different types of infections. These infections are called opportunistic because they have an opportunity to invade the body when the immune defenses are weak. HIV infection also increases the risk of certain cancers, illnesses of the brain and nerves, body wasting, and death. The entire spectrum of symptoms and illnesses that can happen when HIV infection significantly depletes the body's immune defenses is called acquired immunodeficiency syndrome or AIDS.

Since 1981, when HIV/AIDS was first recognized as a new illness, scientists have learned much about how a person becomes infected with HIV. The virus is spread through contact with an infected person's body fluids, especially through blood, semen and vaginal fluids. Once inside the body, HIV particles invade CD4 lymphocytes and use the cells' own genetic material to produce billions of new HIV particles. These new particles cause the infected CD4 cell to burst (lyse). The new particles can then enter the bloodstream and infect other cells. Once someone is infected with HIV, the number of their normal CD4 cells continues to decrease.

Eventually, the number of normal CD4 cells drops below the threshold level needed to defend the body against infections, and the person develops AIDS. Doctors used to think that HIV was inactive (dormant or latent) between the initial infection and the diagnosis of AIDS. We now know that HIV is active, copying itself and killing CD4 cells from the time the infection starts through and beyond the diagnosis of AIDS.

Within the past 2 decades, about 60 million people worldwide have become infected with HIV. More than 25 million have died. More than 90% of these people live in developing countries. In some parts of Africa, more than half of adult deaths are caused by HIV infection, leaving millions of children orphaned after their parents died of AIDS. In the United States, as of the end of 2005, there were more than 988,000 cases of AIDS reported, with over 530,000 deaths, including over 6,000 children. HIV rates are increasing most rapidly among minority populations. The infection occurs 6 times as often in African-Americans and 3 times as often in Hispanics compared with whites.

In its early stages, HIV infection has no symptoms or causes only a flulike illness with many of the following symptoms: fever, sore throat, rash, nausea and vomiting, diarrhea, fatigue, swollen lymph nodes, muscle aches, headaches, and joint pain. Although 50% to 90% of people experience symptoms within the first few weeks of contracting HIV infection, most people and doctors dismiss the illness as a routine cold or flu. In a small number of cases, this early stage of infection may progress to meningitis (inflammation of membranes covering the brain) or severe flulike symptoms that require hospitalization.

As the number of CD4 cells drops below normal (800 to 1,200 cells per cubic millimeter of blood), the person may begin to develop swollen lymph nodes and skin problems, such as seborrheic dermatitis (dandruff), new or worsening psoriasis , and minor infections. Ulcers can develop around the mouth.

Over the next few years, as CD4 cells continue to die, skin problems and mouth ulcers develop more often. Recurring herpes and varicella-zoster infections (shingles) can occur. Many people develop diarrhea, fever, unexplained weight loss, joint and muscle pain, and fatigue. Old tuberculosis infections may reactivate even before AIDS develops. (Tuberculosis is one of the most common HIV/AIDS-related infections in the developing world.)

Finally, with further decreases in the levels of CD4 cells, the person develops AIDS. In an HIV-infected person, some signs that AIDS has developed are:

• The CD4 cell count has decreased to fewer than 200 cells per cubic milliliter of blood.



• A particular type of opportunistic infection (classified as an AIDS-defining condition) has developed, indicating that the immune system is severely weakened. These infections include certain types of pneumonia, diarrhea, eye infections and meningitis. Some of the microbes that can cause these opportunistic infections include Candida, cryptococcosis, cytomegalovirus, herpes simplex virus, Mycobacterium avium complex and Pneumocystis jiroveci (formerly called Pneumocystis carinii). The person also can develop fungal infections specific to certain areas of the United States, such as histoplasmosis and coccidioidomycosis.



• A particular type of tumor has developed (classified as an AIDS-defining condion) indicating that the immune system is severely weakened. These cancers include cervical cancer, Kaposi's sarcoma (a cancer causing round, reddish spots in the skin and mouth), certain types of non-Hodgkin's lymphoma and brain lymphoma.



• An AIDS-related brain illness has developed, including HIV encephalopathy (AIDS dementia) or progressive multifocal leukoencephalopathy.



• There is severe body wasting (HIV wasting syndrome).



• There is an AIDS-related lung illness, such as pulmonary lymphoid hyperplasia or lymphoid interstitial pneumonia (usually seen only in children).

Your doctor will ask about possible HIV risk factors, such as previous sexual partners, intravenous drug use, blood transfusion and occupational exposure to blood. Your doctor will ask about a variety of symptoms, such as fever, weight loss, muscle and joint aches, fatigue and headache, and about medical problems you may have had, such as skin rashes or infections, sinusitis, pneumonia, and yeast infections. This typically is followed by a complete physical examination. During the exam, your doctor will look for a thick, white coating on your tongue called thrush (infection with Candida fungus), skin abnormalities and swollen lymph nodes.

HIV testing can be done with a blood test done in your doctor's office or in an anonymous clinic. The initial screening test is called enzyme linked immunosorbent assay (ELISA). It detects disease-fighting proteins in your immune system (antibodies) specific to HIV. A Western blot test, which also measures the body's response to HIV, is more accurate, and is done to confirm the diagnosis. Neither the ELISA nor Western blot is accurate immediately after exposure to the HIV virus. It can take a few months for these tests to become positive.

The period between infection with HIV and the development of positive test results on ELISA and Western blot is called the window period. This term refers to the window of time between getting the HIV infection and the ability to detect the body's response to infection with one of these two tests. If the test results are positive, another test, called the HIV RNA blood test, can measure the amount of HIV virus in the blood (viral load). Once you have been diagnosed with HIV, your doctor will determine how much the virus has weakened your immune system by ordering a blood test to check your CD4 cell count. If you have fewer than 200 cells per cubic milliliter of blood, this indicates that you have AIDS. You also may have tests to diagnose AIDS-related conditions, including opportunistic infections, or tumors, depending on your symptoms.

HIV infection is a lifelong illness.

HIV infection can be passed from person to person in any of the following ways:

• Unprotected sexual intercourse (heterosexual or homosexual)
• Oral sex with an infected person
• A contaminated blood transfusion (very rare in the United States since 1985, when blood supplies started being tested for HIV)
• Needle sharing (if one intravenous drug user is infected)
• Occupational exposure (needle stick with infected blood)
• Artificial insemination with infected semen
• Organ transplant taken from an HIV-infected donor

Newborns can catch HIV infection from their mothers before or during birth or through breastfeeding.

There is no evidence that HIV can be spread through the following: kissing; sharing food utensils, towels or bedding; swimming in pools; using toilet seats; using telephones; or having mosquito or other insect bites.

Although several HIV vaccines are being tested, none has been approved. You can decrease your chances of being infected with HIV by avoiding high-risk behaviors. To decrease the risk of HIV infection:

• Don't have sex, or have sex with only one partner who is also committed to having sex with only you.
• Use condoms with each act of sexual intercourse.
• If you use intravenous drugs, never share needles.
• If you are a health care worker, strictly follow universal precautions (the established infection-control procedures to avoid contact with bodily fluids).
• If you are a woman thinking about becoming pregnant, have a test for HIV beforehand, especially if you have a history of behaviors that put you at risk of HIV infection. Pregnant women who are HIV-positive need special prenatal care and medications to decrease the risk that HIV will pass to their newborn babies.

Your doctor may choose a combination of drugs called highly active antiretroviral therapy (HAART) to fight your HIV infection. By using several drugs simultaneously (often called a drug cocktail), your doctor hopes to increase the effectiveness of AIDS treatment by attacking HIV at multiple points. Combining drugs also limits the risk that HIV will become resistant to drugs, which would make the drugs ineffective.

Many studies have shown that people with high levels of virus in the blood (the viral load) will progress more rapidly to AIDS. Though it is not possible to completely clear the virus from the body, the goal of HAART is to suppress the virus so that it cannot be detected in the blood, to increase the CD4 count and to strengthen the weakened immune system. Currently available antiretroviral drugs include:

• Nucleoside reverse transcriptase inhibitors, such as zidovudine (Retrovir, AZT), didanosine (Videx, ddI), stavudine (Zerit, d4T), abacavir (ABC), and lamivudine (Epivir, 3TC). Tenofovir (Viread) is a commonly prescribed drug in a related family (nucleotide reverse transcriptase inhibitors). There is also a combination pill of lamivudine and zidovudine (called Combivir) and emtricitabine and tenofovir (called Truvada).



• Protease inhibitors, such as saquinavir (Invirase, Fortovase), ritonavir (Norvir), indinavir (Crixivan), nelfinavir (Viracept), amprenavir (Agenerase), fosamprenavir (Lexiva), Tipranavir (Aptivus) and Atazanvir (Reyataz). The protease inhibitors are often boosted with ritonavir to increase their potency. Lopinavir and ritonavir are combined into one pill (Kaletra) for this purpose.



• Non-nucleoside reverse transcriptase inhibitors, such as nevirapine (Viramune) and efavirenz (Sustiva)



• Fusion inhibitors, such as enfuvirtide (Fuzeon)

One common treatment approach is HAART, which combines three nucleoside analogues, two nucleoside analogues and one protease inhibitor, or two nucleoside analogues and one non-nucleoside reverse transcriptase inhibitor. Many other variations exist. Many of these drugs have side effects, such as nausea and diarrhea. In addition, some have severe drug interactions with commonly used medications. Fusion inhibitors are reserved for patients who are infected with a drug-resistant HIV strain.

In addition to HAART, people with low CD4 counts should take drugs to prevent the development of opportunistic infections. For example, people with CD4 cell counts below 200 cells per milliliter of blood should take trimethoprim-sulfamethoxazole (Bactrim) to protect themselves against Pneumocystis pneumonia.

Call your doctor immediately if you believe that you have been exposed to the body fluids of someone who has HIV or AIDS. If your exposure is felt to be significant, your doctor will recommend that you take post-exposure prophylaxis, which is a combination of HAART to decrease your risk of getting HIV/AIDS. These drugs work best when they are taken within three days of the exposure. You should also speak with your doctor if you feel that you have a risk of HIV infection, so that you can be tested for the disease.

The average time for HIV infection to progress to AIDS is 10 to 11 years for people who do not take HAART. However, in about 20% of people with HIV infection, usually those with the highest viral load, AIDS develops sooner (5 years after infection). In 2% of people, it develops later (more than 12 years after infection).

Once HIV infection has progressed to AIDS, there is an increased risk of death that varies dramatically from person to person. For example, some people with AIDS have died shortly after they were diagnosed, whereas others have lived 12 years or more. Since 1995, when HAART became available, the number of deaths from AIDS has decreased by over 80% in the United States. The rate of AIDS hospitalizations and complications has also substanially declined.

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National Pediatrics AIDS Network
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