HIV Infection and AIDS: An Overview OVERVIEW AIDS was first reported in the United States in 1981 and has since become a major worldwide epidemic. AIDS is caused by the human immunodeficiency virus, or HIV. By killing or damaging cells of the body's immune system, HIV progressively destroys the body's ability to fight infections and certain cancers. People diagnosed with AIDS may get life-threatening diseases called opportunistic infections. These infections are caused by microbes such as viruses or bacteria that usually do not make healthy people sick. Since 1981, more than 980,000 cases of AIDS have been reported in the United States to the Centers for Disease Control and Prevention (CDC). According to CDC, more than 1,000,000 Americans may be infected with HIV, one-quarter of whom are unaware of their infection. The epidemic is growing most rapidly among minority populations and is a leading killer of African-American males ages 25 to 44. According, AIDS affects nearly seven times more African Americans and three times more Hispanics than whites. In recent years, an increasing number of African-American women and children are being affected by HIV/AIDS. TRANSMISSION HIV is spread most often through unprotected sex with an infected partner. The virus can enter the body through the lining of the vagina, vulva, penis, rectum, or mouth during sex. Risky behavior HIV can infect anyone who practices risky behaviors such as Sharing drug needles or syringes Having sexual contact, including oral sexual contact, with an infected person without using a condom Having sexual contact with someone whose HIV status is unknown Infected blood HIV also is spread through contact with infected blood. Before donated blood was screened for evidence of HIV infection and before heat-treating techniques to destroy HIV in blood products were introduced, HIV was transmitted through transfusions of contaminated blood or blood components. Today, because of blood screening and heat treatment, the risk of getting HIV from blood transfusions is extremely small. Contaminated needles HIV is often spread among injection drug users when they share needles or syringes contaminated with very small quantities of blood from someone infected with the virus. It is rare for a patient to be the source of HIV transmitted to a healthcare provider or vice versa by accidental sticks with contaminated needles or other medical instruments. Mother to child Women can transmit HIV to their babies during pregnancy or birth. Approximately one-quarter to one-third of all untreated pregnant women infected with HIV will pass the infection to their babies. HIV also can be spread to babies through the breast milk of mothers infected with the virus. If the mother takes certain drugs during pregnancy, she can significantly reduce the chances that her baby will get infected with HIV. If healthcare providers treat HIV-infected pregnant women and deliver their babies by cesarean section, the chances of the baby being infected can be reduced to a rate of 1 percent. HIV infection of newborns has been almost eradicated in the United States because of appropriate treatment. A study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) in Uganda found a highly effective and safe drug for preventing transmission of HIV from an infected mother to her newborn. Independent studies have also confirmed this finding. This regimen is more affordable and practical than any other examined to date. Results from the study show that a single oral dose of the antiretroviral drug nevirapine (NVP) given to an HIV-infected woman in labor and another to her baby within 3 days of birth reduces the transmission rate of HIV by half compared with a similar short course of AZT (azidothymidine). Saliva Although researchers have found HIV in the saliva of infected people, there is no evidence that the virus is spread by contact with saliva. Laboratory studies reveal that saliva has natural properties that limit the power of HIV to infect, and the amount of virus in saliva appears to be very low. Research studies of people infected with HIV have found no evidence that the virus is spread to others through saliva by kissing. The lining of the mouth, however, can be infected by HIV, and instances of HIV transmission through oral intercourse have been reported. Scientists have found no evidence that HIV is spread through sweat, tears, urine, or feces. Casual contact Studies of families of HIV-infected people have shown clearly that HIV is not spread through casual contact such as the sharing of food utensils, towels and bedding, swimming pools, telephones, or toilet seats. HIV is not spread by biting insects such as mosquitoes or bedbugs. Sexually transmitted infections People with a sexually transmitted infection, such as syphilis, genital herpes, chlamydia, gonorrhea, or bacterial vaginosis, may be more susceptible to getting HIV infection during sex with infected partners. SYMPTOMS Early symptoms Many people will not have any symptoms when they first become infected with HIV. They may, however, have a flu-like illness within a month or two after exposure to the virus. This illness may include Fever Headache Tiredness Enlarged lymph nodes (glands of the immune system easily felt in the neck and groin) These symptoms usually disappear within a week to a month and are often mistaken for those of another viral infection. During this period, people are very infectious, and HIV is present in large quantities in genital fluids. Later symptoms More persistent or severe symptoms may not appear for 10 years or more after HIV first enters the body in adults, or within 2 years in children born with HIV infection. This period of asymptomatic infection varies greatly in each person. Some people may begin to have symptoms within a few months, while others may be symptom-free for more than 10 years. Even during the asymptomatic period, the virus is actively multiplying, infecting, and killing cells of the immune system. The virus can also hide within infected cells and be inactive. The most obvious effect of HIV infection is a decline in the number of CD4 positive T (CD4+) cells found in the blood-the immune system's key infection fighters. The virus slowly disables or destroys these cells without causing symptoms. As the immune system becomes more debilitated, a variety of complications start to take over. For many people, the first signs of infection are large lymph nodes, or swollen glands that may be enlarged for more than 3 months. Other symptoms often experienced months to years before the onset of AIDS include Lack of energy Weight loss Frequent fevers and sweats Persistent or frequent yeast infections (oral or vaginal) Persistent skin rashes or flaky skin Pelvic inflammatory disease in women that does not respond to treatment Short-term memory loss Some people develop frequent and severe herpes infections that cause mouth, genital, or anal sores, or a painful nerve disease called shingles. Children may grow slowly or get sick a frequently. WHAT IS AIDS? Symptoms of opportunistic infections common in people with AIDS include Coughing and shortness of breath Seizures and lack of coordination Difficult or painful swallowing Mental symptoms such as confusion and forgetfulness Severe and persistent diarrhea Fever Vision loss Nausea, abdominal cramps, and vomiting Weight loss and extreme fatigue Severe headaches Coma Children with AIDS may get the same opportunistic infections as do adults with the disease. In addition, they also may have severe forms of the typically common childhood bacterial infections, such as conjunctivitis (pink eye), ear infections, and tonsillitis. People with AIDS are also particularly prone to developing various cancers, especially those caused by viruses such as Kaposi's sarcoma and cervical cancer, or cancers of the immune system known as lymphomas. These cancers are usually more aggressive and difficult to treat in people with AIDS. Signs of Kaposi's sarcoma in light-skinned people are round brown, reddish, or purple spots that develop in the skin or in the mouth. In dark-skinned people, the spots are more pigmented. During the course of HIV infection, most people experience a gradual decline in the number of CD4+ T cells, although some may have abrupt and dramatic drops in their CD4+ T-cell counts. A person with CD4+ T cells above 200 may experience some of the early symptoms of HIV disease. Others may have no symptoms even though their CD4+ T-cell count is below 200. Many people are so debilitated by the symptoms of AIDS that they cannot hold a steady job or do household chores. Other people with AIDS may experience phases of intense life-threatening illness followed by phases in which they function normally. A small number of people first infected with HIV 10 or more years ago have not developed symptoms of AIDS. Scientists are trying to determine what factors may account for the lack of progression to AIDS in some people, such as Whether their immune systems have particular characteristics Whether they were infected with a less aggressive strain of the virus If their genes may protect them from the effects of HIV Scientists hope that understanding the body's natural method of controlling infection may lead to ideas for protective HIV vaccines and use of vaccines to prevent the disease from progressing. DIAGNOSIS Because early HIV infection often causes no symptoms, a healthcare provider usually can diagnose it by testing blood for the presence of antibodies (disease-fighting proteins) to HIV. HIV antibodies generally do not reach noticeable levels in the blood for 1 to 3 months after infection. It may take the antibodies as long as 6 months to be produced in quantities large enough to show up in standard blood tests. Hence, to determine whether a person has been recently infected (acute infection), a healthcare provider can screen blood for the presence of HIV genetic material. Direct screening of HIV is extremely critical in order to prevent transmission of HIV from recently infected individuals. Anyone who has been exposed to the virus should get an HIV test as soon as the immune system is likely to develop antibodies to the virus-within 6 weeks to 12 months after possible exposure to the virus. By getting tested early, a healthcare provider can give advice to an infected person about when to start treatment to help the immune system combat HIV and help prevent the emergence of certain opportunistic infections (see section on treatment). Early testing also alerts an infect person to avoid high-risk behaviors that could spread the virus to others. Most healthcare providers can do HIV testing and will usually offer counseling at the same time. Of course, testing can be done anonymously at many sites if a person is concerned about confidentiality. Healthcare providers diagnose HIV infection by using two different types of antibody tests: ELISA (enzyme-linked immunosorbent assay) and Western blot. If a person is highly likely to be infected with HIV but has tested negative for both tests, a healthcare provider may request additional tests. A person also may be told to repeat antibody testing at a later date, when antibodies to HIV are more likely to have developed. Babies born to mothers infected with HIV may or may not be infected with the virus, but all carry their mothers' antibodies to HIV for several months. If these babies lack symptoms, healthcare providers cannot make a definitive diagnosis of HIV infection using standard antibody tests. Instead, they are using new technologies to detect HIV and more accurately determine HIV infection in infants between ages 3 months and 15 months. Researchers are evaluating a number of blood tests to determine which ones are best for diagnosing HIV infection in babies younger than 3 months. TREATMENT When AIDS first surfaced in the United States, there were no drugs to combat the underlying immune deficiency and few treatments existed for the opportunistic diseases that resulted. Researchers, however, have developed drugs to fight both HIV infection and its associated infections and cancers. HIV infection The Food and Drug Administration (FDA) has approved a number of drugs for treating HIV infection. The first group of drugs, called reverse transcriptase (RT) inhibitors, interrupts an early stage of the virus making copies of itself. Nucleoside/nucleotide RT inhibitors are faulty DNA building blocks. When these faulty pieces are incorporated into the HIV DNA (during the process when the HIV RNA is converted to HIV DNA), the DNA chain cannot be completed, thereby blocking HIV from replicating in a cell. Non-nucleoside RT inhibitors bind to reverse transcriptase, interfering with its ability to convert the HIV RNA into HIV DNA. This class of drugs may slow the spread of HIV in the body and delay the start of opportunistic infections. FDA has approved a second class of drugs for treating HIV infection. These drugs, called protease inhibitors, interrupt the virus from making copies of itself at a later step in its life cycle. FDA also has introduced a third new class of drugs, known at fusion inhibitors, to treat HIV infection. Fuzeon (enfuvirtide or T-20), the first approved fusion inhibitor, works by interfering with the ability of HIV-1 to enter into cells by blocking the merging of the virus with the cell membranes. This inhibition blocks HIV's ability to enter and infect the human immune cells. Fuzeon is designed for use in combination with other anti-HIV treatments. It reduces the level of HIV infection in the blood and may be effective against HIV that has become resistant to current antiviral treatment schedules. Because HIV can become resistant to any of these drugs, healthcare providers must use a combination treatment to effectively suppress the virus. When multiple drugs (three or more) are used in combination, it is referred to as highly active antiretroviral therapy, or HAART, and can be used by people who are newly infected with HIV as well as people with AIDS. Recently, FDA approved the first one-a-day three drug-combination pill called Atripla. Researchers have credited HAART as being a major factor in significantly reducing the number of deaths from AIDS in this country. While HAART is not a cure for AIDS, it has greatly improved the health of many people with AIDS and it reduces the amount of virus circulating in the blood to nearly undetectable levels. Researchers, however, have shown that HIV remains present in hiding places, such as the lymph nodes, brain, testes, and retina of the eye, even in people who have been treated. Side effects Despite the beneficial effects of HAART, there are side effects associated with the use of antiviral drugs that can be severe. Some of the nucleoside RT inhibitors may cause a decrease of red or white blood cells, especially when taken in the later stages of the disease. Some may also cause inflammation of the pancreas and painful nerve damage. There have been reports of complications and other severe reactions, including death, to some of the antiretroviral nucleoside analogs when used alone or in combination. Therefore, health experts recommend that anyone on antiretroviral therapy be routinely seen and followed by their healthcare provider. The most common side effects associated with protease inhibitors include nausea, diarrhea, and other gastrointestinal symptoms. In addition, protease inhibitors can interact with other drugs resulting in serious side effects. Fuzeon may also cause severe allergic reactions such as pneumonia, trouble breathing, chills and fever, skin rash, blood in urine, vomiting, and low blood pressure. Local skin reactions are also possible since it is given as an injection underneath the skin. People taking HIV drugs should contact their healthcare providers immediately if they have any of these symptoms. Opportunistic infections A number of available drugs help treat opportunistic infections. These drugs include Foscarnet and ganciclovir to treat CMV (cytomegalovirus) eye infections Fluconazole to treat yeast and other fungal infections TMP/SMX (trimethoprim/sulfamethoxazole) or pentamidine to treat PCP (Pneumocystis carinii pneumonia) Cancers Healthcare providers use radiation, chemotherapy, or injections of alpha interferon-a genetically engineered protein that occurs naturally in the human body-to treat Kaposi's sarcoma or other cancers associated with HIV infection. PREVENTION Because there is no vaccine for HIV, the only way people can prevent infection with the virus is to avoid behaviors putting them at risk of infection, such as sharing needles and having unprotected sex. Many people infected with HIV have no symptoms. Therefore, there is no way of knowing with certainty whether a sexual partner is infected unless he or she has repeatedly tested negative for the virus and has not engaged in any risky behavior. Abstaining from having sex or use male latex condoms or female polyurethane condoms may offer partial protection, during oral, anal, or vaginal sex. Only water-based lubricants should be used with male latex condoms. Although some laboratory evidence shows that spermicides can kill HIV, researchers have not found that these products can prevent a person from getting HIV. Recently, NIAID-supported two studies that found adult male medical circumcision reduces a man's risk of acquiring HIV infection by approximately 50 percent. The studies, conducted in Uganda and Kenya, pertain only to heterosexual transmission. As with most prevention strategies, adult male medical circumcision is not completely effective at preventing HIV transmission. Circumcision will be most effective when it is part of a more complete prevention strategy including the ABCs (Abstinence, Be Faithful, Use Condoms) of HIV prevention.