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Harvard Commentaries
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Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School


HIV/AIDS


December 19, 2011

Sexually Transmitted Diseases
8799
HIV / AIDS

 

What Is It?

The human immunodeficiency virus (HIV) weakens the body's immune defenses by destroying CD4 (T-cell) lymphocytes, which are white blood cells that normally help guard the body against attacks by bacteria, viruses and other germs. When HIV destroys CD4 cells, the body becomes vulnerable to many different types of infections. These infections are called "opportunistic" because usually they only have the 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 range of symptoms and illnesses that can happen when HIV infection severely weakens the body's immune defenses is called acquired immunodeficiency syndrome or AIDS.

Since 1981, when doctors first recognized HIV/AIDS 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. Therefore, HIV can be transmitted through sex (anal, vaginal and oral), contaminated blood (by sharing or accidentally being stuck with a contaminated needle, or through transfusions before blood products started being screened for HIV in 1985) or by being born to a mother who is infected with HIV.

Once inside the body, HIV particles invade CD4 cells and use the cells' own building machinery and materials to produce billions of new HIV particles. These new particles cause the infected CD4 cells 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 CD4 cells continues to decrease. HIV is actively copying itself and killing CD4 cells from the time the infection starts. Eventually, the number of CD4 cells drops below the threshold level needed to defend the body against infections, and the person develops AIDS.

An estimated 34 million people in the world are living with HIV/AIDS. More than 90% of these people live in developing countries. About 2.6 million people are newly infected per year.

Although survival has improved dramatically in developed countries, that is not the case in many under developed countries. In some parts of Africa, more than half of adult deaths are AIDS-related, leaving millions of children orphaned after their parents died of AIDS.

At the end of 2009, there were more than 1,100,000 people living with HIV in the United States (U.S.).

While African Americans are 12% of the population, nearly 50% of those with HIV in the U.S. are African American. African American men are six times more likely to be infected with HIV than white men and African American women are 18 times more likely to be infected with HIV than white women.

In the U.S. today, about 25% of HIV infections are in women. Most of them were infected through sex with an infected man.

The CDC estimates that about 20% of people in the U.S. who have HIV don't know they are infected. It is important for people infected with HIV to know their status so they can get medical treatment before AIDS develops and they can take steps to prevent passing the virus to someone else.

Symptoms

In its early stages, HIV infection may have no symptoms or may cause a flu-like illness with some of the following symptoms: fever, sore throat, rash, nausea and vomiting, diarrhea, fatigue, swollen lymph nodes, muscle aches, headaches, and joint pain. Although most people experience symptoms within the first few weeks of being infected with HIV, 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 flu-like symptoms that require hospitalization.

As the number of CD4 cells drops below normal (500 to 2,000 cells per cubic millimeter of blood), the person may begin to develop swollen lymph nodes and skin problems, such as varicella-zoster (shingles), seborrheic dermatitis (dandruff), new or worsening psoriasis, and minor infections. Ulcers can develop around the mouth and herpes outbreaks (oral or genital) may become more frequent.

Over the next few years, as CD4 cells continue to die, skin problems and mouth ulcers develop more often. 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. According to the CDC, for an HIV-infected person, some signs that AIDS has developed (known as AIDS-defining conditions) are:

  • The CD4 cell count has decreased to fewer than 200 cells per cubic milliliter of blood.
  • An opportunistic infection has developed, indicating that the immune system is severely weakened. These types of infections include specific causes of pneumonia, diarrhea, eye infections and meningitis. Some of the causes of these opportunistic infections include Cryptococcus, reactivation of cytomegalovirus, reactivation of toxoplasma in the brain, wide-spread infection with Mycobacterium avium complex and Pneumocystis jiroveci (formerly called Pneumocystis carinii) in the lungs.
  • A type of cancer has developed that shows that the immune system is severely weakened. For those who are infected with HIV, these cancers can include advanced 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 (PML) that is caused by the JC virus.
  • 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).

Diagnosis

Your doctor will ask about possible HIV risk factors, such as previous sexual partners, intravenous drug use, blood transfusion and occupational exposure to blood, such as accidentally being stuck by needles. Your doctor might 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 in the past like sexually transmitted infections or hepatitis. 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), any skin abnormalities and swollen lymph nodes. To make the diagnosis of HIV infection, however, laboratory tests are needed.

HIV testing can be done with a blood test done in your doctor's office or in an anonymous clinic. In some places, the test can be done with an oral swab and uses saliva instead of blood. The initial screening test is called an enzyme immunoassay (EIA or sometimes an enzyme linked immunosorbent assay [ELISA]). The EIA detects disease-fighting proteins that are made by your immune system called antibodies: The EIA test for HIV infection looks for antibodies made by your immune system specifically against the virus. If the EIA is positive, a Western blot test, which also measures the body's antibody response to HIV but is more accurate than the EIA, is done to confirm the diagnosis. There are several causes of false positive EIAs, but a false positive Western blot is very rare.

Neither the EIA nor the Western blot is accurate immediately after a person is infected with 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 for antibodies 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 (the development of antibodies). Although it is possible to measure the virus directly in the blood (viral load test), this test is used for diagnosis only in special circumstances.

If you have been diagnosed with HIV, your doctor will determine if 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 means that you have AIDS. You also may have tests to diagnose AIDS-related conditions, including opportunistic infections, or cancers, depending on your symptoms.

Expected Duration

HIV infection is a lifelong illness. There is no known cure for HIV. However, advances in treatment have changed the thinking about HIV as a fatal disease. Doctors now consider HIV a chronic condition that can be controlled with medications and healthy life style choices.

Prevention

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

  • Unprotected sexual intercourse (heterosexual or homosexual anal, vaginal or oral sex) with an infected person
  • A contaminated transfusion (extremely rare in the United States since 1985, when blood products 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. Casual contact in the home, workplace or public spaces poses no risk of HIV transmission.

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:

  • Have sex with only one partner who is also committed to having sex with only you. Consider getting tested together for HIV.
  • Use condoms with each act of sexual intercourse.
  • If you use intravenous drugs or inject steroids, 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 or your partner have a history of behaviors that could have 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.
  • If you believe you may have been exposed to HIV (through sexual contact or through exposure to blood, such as through a needle containing infected blood), medications may help prevent HIV infection before it takes hold in the body. The medication should be taken as soon as possible but not more than 72 hours (3 days) after exposure. If you think you may have been exposed, call your doctor or go directly for urgent care immediately.

Treatment

The International AIDS Society - USA Panel recommends that patients start taking antiviral medications (antiretrovirals) before the CD4 count falls below 350 cells per cubic milliliter of blood. Many experts suggest using 500 as the benchmark. Most recently, some doctors are recommending starting treatment immediately after the diagnosis is confirmed. The exact timing will depend on many factors, risks and benefits that should be discussed by the patient and the doctor.

If the decision is made to start treatment, your doctor will choose a combination of drugs called antiretrovirals to fight your HIV infection. To control the reproduction of HIV in the body, several medications must be used together (often called a drug cocktail or highly active antiretroviral therapy (HAART). These medications attack HIV at multiple points in its growth cycle and are more effective in suppressing the virus. Combining drugs also limits the risk that HIV will become resistant to drugs, which would mean the drugs are powerless against this resistant strain of HIV.

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 clear the virus from the body completely, the goal of treatment is to keep the virus from reproducing. This can be seen when the viral load test cannot detected the HIV virus in the bloodstream (the virus never goes away, just goes to very low levels). When the virus is not reproducing quickly, it is less likely to kill CD4 cells. As the CD4 cell count increases, the immune system regains strength.

There are many available antiretroviral medications in the United States today. Many of these can be prescribed in combination form making the total number of different "pills" available closer to 30. Many medications have two or three names and may be referred to by the generic name, trade name or a three letter abbreviation (for example, AZT is also known by its generic name, zidovudine, and by its trade name, Retrovir). Currently available antiretroviral drugs include:

  • Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (Retrovir, AZT), didanosine (Videx, ddI), stavudine (Zerit, d4T), abacavir (Ziagen, ABC), emtricitabine (Emtriva, FTC) and lamivudine (Epivir, 3TC) block HIV reproduction at the virus' "reverse transcriptase." Tenofovir (Viread) is a commonly prescribed drug in a related family (nucleotide reverse transcriptase inhibitors). There are many NRTI combination pills including lamivudine and zidovudine (called Combivir) and emtricitabine and tenofovir (called Truvada).

  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine (Viramune) and efavirenz (Sustiva) act on the same HIV reverse transcriptase that the NRTIs block, but at a different location.

  • Protease inhibitors (PIs), such as atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase), , , and Tipranavir (Aptivus) block the assembly of new HIV virus particles (they inhibit the virus' "protease"). The PIs are often "boosted" with ritonavir to increase their potency. Lopinavir and ritonavir are combined into one pill (Kaletra) for this purpose.

  • Cell entrance blockers. A fusion inhibitor called enfuvirtide (Fuzeon) and a CCR5 co-receptor antagonist called maraviroc (Selzentry) are currently the only medications available that block HIV from getting inside the cell in the first place. These medications block the virus at the cell surface. Enfuvirtide is only available in injectable form.

  • Integrase inhibitor. Raltegravir (Isentress) is the only medication available today that blocks the "integration" of the virus' genetic material with the cell's genetic material. This blocks HIV from reproducing inside the cell.

Numerous combinations can be made depending on patient and doctor preference. Because many of these drugs have side effects, such as nausea and diarrhea, the exact medications prescribed for a particular person may depend on side effects (which will be different from person to person).

A commonly recommend initial therapy is a combination of the NNRTI efavirenz (Sustiva) and two NRTIs. A potential choice for people who are likely to miss doses of medication is a combination pill called Atripla. It contains efavirenz, emtricitabine and tenofovir. Atripla is taken as one pill, once per day.

It is very important to tell your doctor about ALL other medications you take (including herbals and non-prescription medications) because there can be serious drug-drug interactions with commonly used medications. Also, no one should take an antiretroviral medication that was not specifically prescribed for them by a health care provider.

In addition to antiretrovirals, 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 (known as Bactrim or Septra) to protect themselves against Pneumocystis pneumonia.

When to Call a Professional

Your doctor can help you protect yourself against HIV. Let your doctor know if you are a man who has sex with men or if you share needles with anyone for any reason (intravenous drugs or steroids, for example). If you are a woman and think your male partner may have risk factors for HIV infection, please let your doctor know. Your doctor can give you information about how to reduce your risk of HIV.

You should also speak with your doctor if you think you may already have HIV infection so that you can be tested for the disease. If you have long-lasting headache, cough, diarrhea, skin sores or are having fevers or losing weight, let your doctor know. Even without any symptoms, the sooner you get tested for HIV, the sooner appropriate treatment can be started that can help you live a long, healthy life.

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 may recommend that you take antiretrovirals that may decrease your risk of getting HIV/AIDS. These drugs work best when they are taken within 72 hours (3 days) of the exposure.

Prognosis

The average time for HIV infection to progress to AIDS is 10 to 11 years for people who do not take antiretrovirals. In people with very high HIV viral load, AIDS may develop sooner (within 5 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.

Because very potent medication against HIV has only been available since 1996, we do not yet know how long people will live with HIV infection if they are tested early and treated appropriately. The outlook, however, is very good, especially for those who begin antiretrovirals at an early stage of the disease. If you are infected with HIV, it is best to find out as soon as possible so that treatment can be started before the immune system is weakened. Since potent antiretrovirals became available in the United States, the number of AIDS-related deaths and hospitalizations has decreased dramatically. The AIDS-related death rate in some parts of the developing world, however, remains staggeringly high due to lack of access to life-saving antiretrovirals.

Additional Info

National Institute of Allergy and Infectious Diseases (NIAID)
Office of Communications & Public Liaison
6610 Rockledge Drive, MSC6612
Bethesda, MD 20892-6612
Phone: 301-496-5717
http://www.niaid.nih.gov/

CDC National Prevention Information Network (NPIN)
National Center for HIV, STD and TB Prevention
P.O. Box 6003
Rockville, MD 20849-6003
Toll-Free: 1-800-458-5231
TTY: 1-800-243-7012
Fax: 1-888-282-7681
http://www.cdcnpin.org/ or
http://www.cdc.gov/hiv/

National Pediatrics AIDS Network
P.O. Box 1032
Boulder, CO 80306
http://www.npan.org/

HIV/AIDS
htmIndexHIV-AIDS
The human immunodeficiency virus (HIV) weakens the body's immune defenses by destroying CD4 (T-cell) lymphocytes, which are white blood cells that normally help guard the body against attacks by bacteria, viruses and other germs.
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2011-12-19
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InteliHealth Medical Content
2013-01-18
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