بحث عن What Is AIDS - بحث علمى عن What Is AIDS كامل ومنسق

بحث عن What Is AIDS - بحث علمى عن What Is AIDS كامل ومنسق

AIDS stands for Acquired Immunodeficiency (or Immune Deficiency) Syndrome. It results from infection with a virus called HIV, which stands for Human Immunodeficiency Virus. This virus infects key cells in the human body called CD4-positive (CD4+) T cells. These cells are part of the body's immune system, whichfights infections and various cancers.

When HIV invades the body's CD4+ T cells, the damaged immune system loses its ability to defend against diseases caused by bacteria, viruses, and other microscopic organisms. A substantial decline in CD4+ T cells also leaves the body vulnerable to certain cancers.
There is no cure for AIDS, but medical treatments can slow down the rate at which HIV weakens the immune system. As with other diseases, early detection offers more options for treatment and preventing complications.
What Is The Difference Between HIV And AIDS?
The term AIDS refers to an advanced stage of HIV infection, when the immune system has sustained substantial damage. Not everyone who has HIV infection develops AIDS.
When HIV progresses to AIDS, however, it has proved to be a universally fatal illness. Few people survive five years from the time they are diagnosed with AIDS, although this is increasing with improvements in treatment techniques.
Experts estimate that about half the people with HIV will develop AIDS within 10 years after becoming infected. This time varies greatly from person to person, however, and can depend on many factors, including a person's health status and health-related behaviors.
People are said to have AIDS when they have certain signs or symptoms specified in guidelines formulated by the U.S. Centers for Disease Control and Prevention (CDC).
The CDC's definition of AIDS includes:
• All HIV-infected people with fewer than 200 CD4+ T cells per cubic millimeter of blood (compared with CD4+ T cell counts of about 1,000 for healthy people)
• People with HIV infection who have at least one of more than two dozen AIDS-associated conditions that are the result of HIV's attack on the immune system
AIDS-associated conditions include:
• Opportunistic infections by bacteria, fungi, and viruses. Opportunistic infections are infections that are rarely seen in healthy people but occur when a person's immune system is weakened.
• The development of certain cancers (including cervical cancer and lymphomas).
• Certain autoimmune disorders.

Most AIDS-associated conditions are rarely serious in
healthy individuals. In people with AIDS, however, these infections are often severe and sometimes fatal because the immune system is so damaged by HIV that the body cannot fight them off.
The History Of AIDS
The symptoms of AIDS were first recognized in the early 1980s:
• In 1981, a rare lung infection called Pneumosystis carinii pneumonia began to appear in homosexual men living in Los Angeles and New York.
• At the same time, cases of a rare tumor called Kaposi's sarcoma were also reported in young homosexual men. These tumors had been previously known to affect elderly men, particularly in parts of Africa. New appearances of the tumors were more aggressive in the young men and appeared on parts of the body other than the skin.
• Other infections associated with weakened immune defenses were also reported in the early 1980s.
Groups most frequently reporting these infections in the early 1980s were homosexuals, intravenous drug users, and people with hemophilia, a blood disorder that requires frequent transfusions. Blood and sexual transmission were therefore suspected as the sources for the spread of the infections.
In 1984, the responsible virus was identified and given a name. In 1986, it was renamed the human immunodeficiency virus (HIV).

Need To Know: Because many of the first cases of AIDS in the United States occurred in homosexual men and intravenous drug users, some people mistakenly believe that other groups of people are not at risk for HIV infection. However, anyone is capable of becoming HIV-infected, regardless of gender, age, or sexual orientation.

• Facts About AIDS As of the year 2000, nearly one million people in the U.S. were confirmed to be HIV-positive. The Centers for Disease Control and Prevention reports that 2.2 million Americans now carry the HIV virus but do not yet have symptoms. Each year, about 40,000 new HIV infections occur in the U.S. AIDS is a leading cause of death for American men and women between the ages of 25 and 44. Through June 2000, 438,795 people in the U.S. had died from AIDS (374,422 men and 64,373 women). By the end of 2000, 36.1 million people worldwide were living with HIV/AIDS, with the vast majority living in developing countries. Through 2000, 21.8 million people worldwide have died from AIDS. Between 1991 and 1996, there were more new cases of AIDS among people older than 50 than those between ages 13 and 49. Today, 11% of all new cases of AIDS in the U.S. are now in people over the age of 50. The HIV carrier rate in the U.S. is now 1 carrier for every 100 to 200 people.

How Is HIV Infection Spread?
HIV infection is spread in three ways:
• Sexual intercourse
• Direct contact with infected blood
• From an infected mother to her unborn child
However, there is much misunderstanding about the ways in which HIV infection is not spread.
Sexual Intercourse
HIV is spread most commonly by sexual contact with an infected partner. The virus can enter the body through the lining of the vagina, penis, rectum, or mouth during sexual relations.
Sexual activities that can result in HIV infection include:
• Sexual intercourse
• Anal sex (heterosexual or homosexual )
• Oral sex (heterosexual or homosexual)
Need To Know: Q: Can HIV be spread through kissing? A: Although studies have found tiny amounts of HIV in the saliva of some people with HIV, researchers have found no evidence that HIV is spread to other people through kissing. However, the CDC recommends against "French" or open-mouthed kissing because of the possibility of contact with blood if the people kissing have any cuts or sores in the mouth.
Direct Contact With Infected Blood

HIV can be spread through direct contact with infected blood:
• Through injected drugs. HIV frequently is spread among users of illegal drugs that are injected. This happens when needles or syringes contaminated with minute quantities of blood of someone infected with the virus are shared.
• In a health-care setting. Transmission from patient to health-care worker or vice-versa - via accidental sticks with contaminated needles or other medical instruments - can occur, but this is rare.
• Through a blood transfusion. Prior to the screening of blood for evidence of HIV infection and before the introduction in 1985 of heat-treating techniques to destroy HIV in blood products, HIV was transmitted through transfusions of contaminated blood or blood components. Today, because of blood screening and heat treatment, the risk of acquiring HIV from such transfusions is extremely small.
From An Infected Mother To Her Unborn Child
Women can transmit HIV to their fetuses 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.
A pregnant woman can greatly reduce the risk of infecting her baby if she takes the anti-HIV drug AZT (also called zidovudine) during her pregnancy. Because the risk of transmission increases with longer delivery times, the risk can be further reduced by delivering the baby by caesarian section , a surgical procedure in which the baby is delivered through an incision in the mother's abdominal wall and uterus. Combining AZT treatment with caesarian delivery can reduce the infection rate to between 1% and 2%.
HIV also can be spread to babies through the breast milk of mothers infected with the virus.
• Women who live in countries where safe alternatives to breast-feeding are readily available and affordable can eliminate the risk of transmitting the virus through breast milk by bottle-feeding their babies.
• In developing countries, however, where such safe alternatives are not readily available or economically feasible, breast-feeding may offer benefits that outweigh the risk of HIV transmission.
How Is HIV Infection Not Spread?
Research indicates that HIV is NOT transmitted by casual contact such as:
• Touching or hugging
• Sharing household items such as utensils, towels, and bedding
• Contact with sweat or tears
• Sharing facilities such as swimming pools, saunas, hot tubs, or toilets with HIV-infected people
• Coughs or sneezes
In short, studies indicate that HIV transmission requires intimate contact with infected blood or body fluids (vaginal secretions, semen, pre-ejaculation fluid, and breast milk). Activities that don't involve the possibility of such contact are regarded as posing no risk of infection.

Need To Know: Q: Is it safe to share a household with an HIV-infected person? A: Studies of families of HIV-infected people have found that HIV is not spread through sharing utensils, towels, bedding, or toilet facilities. Behaviors that increase the likelihood of contact with blood from an HIV-infected person, such as sharing a razor or toothbrush, should be avoided.

A Brief History of the Emergence of AIDS

In 1981, clinical investigators in New York and California observed among young, previously healthy, homosexual men an unusual clustering of cases of rare diseases, notably Kaposi's sarcoma (KS) and opportunistic infections such as Pneumocystis carinii pneumonia (PCP), as well as cases of unexplained, persistent lymphadenopathy (CDC, 1981a,b, 1982a; Masur et al., 1981; Gottlieb et al., 1981; Friedman-Kien, 1981). It soon became evident that these men had a common immunologic deficit, an impairment in cell-mediated immunity resulting from a significant loss of "T-helper" cells, which bear the CD4 marker (Gottlieb et al., 1981; Masur et al., 1981; Siegal et al., 1981; Ammann et al., 1983a).
The widespread occurrence of KS and PCP in young people with no underlying disease or history of immunosuppressive therapy was unprecedented. Searches of the medical literature, autopsy records and tumor registries revealed that these diseases previously had occurred at very low levels in the United States (CDC, 1981b; CDC, 1982f).
KS, a very rare skin neoplasm, had affected mostly older men of Mediterranean origin or cancer or transplant patients undergoing immunosuppressive therapy (Gange and Jones, 1978; Safai and Good, 1981). Before the AIDS epidemic, the annual incidence of Kaposi's sarcoma in the United States was 0.02 to 0.06 per 100,000 population (Rothman, 1962a; Oettle, 1962). In addition, a more aggressive form of KS that generally occurred in younger individuals was seen in certain parts of Africa (Rothman, 1962b; Safai, 1984a). By 1984, never-married men in San Francisco were found to be 2,000 times more likely to develop KS than during the years 1973 to 1979 (Williams et al., 1994). As of Dec. 31, 1994, 36,693 patients with AIDS in the United States with a definitive diagnosis of KS had been reported to the CDC (CDC, 1995b).
PCP, a lung infection caused by a pathogen to which most individuals are exposed with no undue consequences, was extremely rare prior to 1981 in individuals other than those receiving immunosuppressive therapy or among the chronically malnourished, such as certain Eastern European children following World War II (Walzer, 1990). A 1967 survey, for example, found only 107 U.S. cases of PCP reported in the medical literature up to that point, virtually all among individuals with underlying immunosuppressive conditions or who had undergone immunosuppressive therapy (Le Clair, 1969). In that year, CDC became the sole supplier in the United States of pentamidine isethionate, then the only recommended PCP therapy, and began collecting data on each PCP case diagnosed and treated in this country. After reviewing requests for pentamidine in the period 1967 to 1970, researchers found only one case of confirmed PCP without a known underlying condition (Walzer et al., 1974). In the period immediately prior to the recognition of AIDS, January 1976 to June 1980, CDC received only one request for pentamidine isethionate to treat an adult in the United States who had PCP and no underlying disease (CDC, 1982f). In 1981 alone, 42 requests for pentamidine were received to treat patients with PCP and no known underlying disorders (CDC, 1982f). By Dec. 31, 1994, 127,626 individuals with AIDS in the United States with definitive diagnoses of PCP had been reported to the CDC (CDC, 1995b).
Another rare opportunistic disease, disseminated infection with the Mycobacterium avium complex (MAC), also was seen frequently in the first AIDS patients (Zakowski et al., 1982; Greene et al., 1982). Prior to 1981, only 32 individuals with disseminated MAC disease had been described in the medical literature (Masur, 1982a). By Dec. 31, 1994, the CDC had received reports of 28,954 U.S. AIDS patients with definitive diagnoses of disseminated MAC (CDC, 1995b).
What Causes AIDS?
HIV is a type of virus called a retrovirus. Like all viruses, it must invade the cells of other organisms to survive and reproduce. HIV multiplies in the human immune system's CD4+ T cells and kills vast numbers of the cells it infects. The result is disease symptoms.

Nice To Know: There are two forms of HIV: HIV-1 is the more common and more potent form. This form of HIV has spread throughout the world. HIV-2, which is less potent that HIV-1, is found predominantly in West Africa. It is also more closely related to two HIV-like viruses found in monkeys. There also are different strains of the virus, which makes it difficult to find one single treatment.
About The Immune System
Our bodies use a natural defense system to protect us from bacteria, fungi, viruses, and other microscopic invaders. This system includes general, nonspecific defenses as well as weapons custom-designed against specific health threats:
• Innate, or nonspecific, immunity is the first line of defense. Our skin, tears, mucus, and saliva, as well as the swelling that occurs after an infection or injury, contain types of immune cells and chemicals that attack disease-causing agents attempting to invade the body.
• Adaptive, or specific, immunity uses specialized cells and proteins called antibodies to attack invaders that get past the first line of defense. These weapons target specific proteins called antigens , found on the surface of the invading organism. The immune system can quickly rally these custom-tailored defenses if this particular invader attacks again.
There are two types of adaptive immune responses:
• The humoral immune response involves the action of specialized antibody-producing white blood cells. The antibodies (proteins produced by the immune system to fight infectious agents such as viruses), which circulate in the blood and other body fluids, can recognize specific antigens (substances that stimulate the production of antibodies). They latch onto the viruses, bacteria, toxins, and other substances that bear these antigens, targeting them for destruction.
• The cell-mediated immune response involves the action of another group of specialized white blood cells that direct and regulate the body's immune responses or directly attack cells that are infected or cancerous.
How Do White Blood Cells Help Fight Disease?
White blood cells, particularly macrophages and B and T lymphocytes , play central roles in the immune system's defenses against viruses and other foreign invaders.
• Macrophages contribute to both nonspecific and specific immune responses. These versatile cells act as scavengers, engulfing and digesting microbes and other foreign material in a cell-eating process called phagocytosis . They also, upon encountering an invading organism, release chemical messengers that ,,,,, other cells of the immune system and summon T lymphocytes to the scene.
• B lymphocytes, or B cells, serve as the body's antibody factories. Each antibody is targeted to recognize and bind to an antigen from a specific invader. When antibodies circulating through blood and body fluids encounter this invader, they mark it for destruction.
• T lymphocytes, or T cells, are part of the cellular immune response. Some T cells, like CD4+ T cells (also called "helper" T cells), direct and regulate the body's immune responses. Others are killer cells that attack cells that are infected or cancerous.
How Does HIV Infection Become Established In The Body?
Researchers have found evidence that immune-system cells called dendritic cells may begin the process of infection. After exposure, these special cells may bind to and carry the virus from the site of infection to the lymph nodes, where other immune system cells become infected.
HIV targets cells in the immune system that display a protein called CD4 on their surface. Such cells are called CD4-positive (CD4+) cells.

Nice To Know: When HIV encounters a CD4+ cell, a protein called gp120 that protrudes from HIV's surface recognizes the CD4 protein and binds tightly to it. Another viral protein, p24, forms a casing that surrounds HIV's genetic material. HIV's genetic material contains the information needed by the virus to infect cells, produce new copies of virus, or cause disease. For example, these genes encode enzymes that HIV requires to reproduce itself. Those enzymes are reverse tran,,,,,,ase , integrase, and protease.

How HIV Causes AIDS

HIV disease is characterized by a gradual deterioration of immune function. Most notably, crucial immune cells called CD4+ T cells are disabled and killed during the typical course of infection. These cells, sometimes called "T-helper cells," play a central role in the immune response, signaling other cells in the immune system to perform their special functions.
A healthy, uninfected person usually has 800 to 1,200 CD4+ T cells per cubic millimeter (mm3) of blood. During HIV infection, the number of these cells in a person's blood progressively declines. When a person's CD4+ T cell count falls below 200/mm3, he or she becomes particularly vulnerable to the opportunistic infections and cancers that typify AIDS, the end stage of HIV disease. People with AIDS often suffer infections of the lungs, intestinal tract, brain, eyes and other organs, as well as debilitating weight loss, diarrhea, neurologic conditions and cancers such as Kaposi's sarcoma and certain types of lymphomas.
Most scientists think that HIV causes AIDS by directly inducing the death of CD4+ T cells or interfering with their normal function, and by triggering other events that weaken a person's immune function. For example, the network of signaling molecules that normally regulates a person's immune response is disrupted during HIV disease, impairing a person's ability to fight other infections. The HIV-mediated destruction of the lymph nodes and related immunologic organs also plays a major role in causing the immunosuppression seen in people with AIDS.

HIV Infection in Women

OVERVIEW
The number of women with HIV (human immunodeficiency virus) infection and AIDS (acquired immunodeficiency syndrome) has been increasing steadily worldwide. By the end of 2003, according to the World Health Organization (WHO), 19.2 million women were living with HIV/AIDS worldwide, accounting for approximately 50 percent of the 40 million adults living with HIV/AIDS.
By the end of 2002, 159,271 adolescent and adult women in the United States were reported as having AIDS. Based on cases reported to the Centers for Disease Control and Prevention (CDC) through December 2002, more than 57,376 women have been infected with HIV. Among adolescent and adult women, the proportion of AIDS cases more than tripled from 7 percent in 1985 to 26 percent in 2002. Nonetheless, AIDS cases in adolescent and adult women have declined by 17 percent and have plateaued in the past 4 years, reflecting the success of antiretroviral therapies in preventing the development of AIDS.
Worldwide, more than 90 percent of all adolescent and adult HIV infections have resulted from heterosexual intercourse. Women are particularly vulnerable to heterosexual transmission of HIV due to substantial mucosal exposure to seminal fluids. This biological fact amplifies the risk of HIV transmission when coupled with the high prevalence of non-consensual sex, sex without condom use, and the unknown and/or high-risk behaviors of their partners.
Younger women are also increasingly being diagnosed with HIV infection, particularly among African-Americans and Hispanics. Through December 2002, women aged 25 and younger accounted for 9.8 percent of the female AIDS cases reported to CDC.
HIV disproportionately affects African-American and Hispanic women. Together they represent less than 25 percent of all U.S. women, yet they account for more than 82 percent of AIDS cases in women.
Women suffer from the same complications of AIDS that afflict men but also suffer gender-specific manifestations of HIV disease, such as recurrent vaginal yeast infections and severe pelvic inflammatory disease, which increase their risk of cervical cancer. Women also exhibit different characteristics from men for many of the same complications of antiretroviral therapy, such as ,,,,bolic abnormalities.
Frequently, women with HIV infection have great difficulty accessing health care, and carry a heavy burden of caring for children and other family members who may also be HIV-infected. They often lack social support and face other challenges that may interfere with their ability to adhere to treatment regimens.

CURRENT RESEARCH
To confront the growing problem of HIV infection and AIDS in women, the National Institute of Allergy and Infectious Diseases (NIAID) has made woman-focused research an important component of the Institute's AIDS research program.
NIAID is studying the course of HIV/AIDS disease in women primarily through two cohort studies: the Women's Interagency HIV Study (WIHS) and the Women and Infant's Transmission Study. Clinical trials to investigate gender-specific differences in disease progression, complications and/or treatment are also being conducted by the Adult AIDS Clinical Trials Group (AACTG), the Pediatric AIDS Clinical Trials Group (PACTG), and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

Natural History and Epidemiological Research
NIAID supports studies in the United States and abroad of the natural history and manifestations of HIV infection in both non-pregnant and pregnant women, as well as the factors that influence the transmission of HIV to women. Investigators are studying the unique features of HIV/AIDS in women and developing treatment regimens for them.
The WIHS, a multi-site, prospective cohort of predominantly minority HIV-infected and uninfected women, is conducting research on the natural history of HIV among women and has increased the number of women enrolled in their study. The increase in participants will enable WIHS to evaluate the natural history and clinical outcomes in the era of highly active antiretroviral therapy, or HAART, such as
• Time to AIDS
• Impact of other infections such as hepatitis C
• Therapy use and treatment effects in women
• Impact of aging on HIV disease
• Impact of hormonal factors on HIV disease
The expansion is now complete, and projects have 2,580 women under active follow-up.
A study conducted in the WIHS compared the rates of AIDS and/or death prior to (October 1994 to April 1996) and after (April 1996 to March 1999) the introduction of HAART (highly active antiretroviral therapy). Mortality declined 21 percent for women with AIDS and 11 percent for those without AIDS at the start of WIHS. The researchers also quantified the level of immune reconstitution and viral suppression. Women with AIDS at study entry saw the greatest improvements in their CD4+/CD8+ cells and viral load.
In another study, WIHS researchers showed that a baseline measurement of serum albumin (the main protein in the blood) was a strong predictor of 3-year survival in HIV-infected women. Women with serum albumin levels in the low-normal range had a higher risk of death compared to those with higher levels of serum albumin. This information could have important implications for women's treatment decisions, and given the low cost and availability of this measurement, it may have applications in resource-poor settings.
Moreover, another study showed that after adjusting for age, serum albumin levels, body mass index, CD4 lymphocyte counts, and HIV-1 RNA levels, higher C-reactive protein levels (> 0.4 mg/dL) were associated with shorter survival. C-reactive protein, an inflammatory marker, may be a useful and inexpensive predictor of HIV disease mortality in women.
In a study co-funded by the National Institute on Drug Abuse and NIAID, researchers found that the initial HIV viral load in women tends to be lower than in men regardless of CD4+ T cell count. Investigators need to do additional research to determine the significance of this finding because the rate of progression to AIDS in women appears to be similar to that in men.

Topical Microbicides
Because HIV is spread predominantly through sexual transmission, the development of chemical, biological, and physical barriers that can be used intravaginally or intrarectally to inactivate HIV and other sexually transmitted infection (STI) pathogens is critically important for controlling HIV infection.
Scientists are developing and testing new chemical and biological compounds that women could apply before intercourse to protect themselves against HIV and other sexually transmitted organisms. These include creams or gels, known as topical microbicides, which ideally would be non-irritating, inexpensive, and unobtrusive. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation. There are several promising investigational topical microbicides, such as PR02000/5 Gel (P), Cellulose Sulfate Gel, and PMPA Gel, currently in clinical trials in the HIV Prevention Trials Network (HPTN).
Less than 10 percent of the participants reported symptoms that could have been attributable to the product, and upon pelvic examination, approximately 90 percent had no visible vaginal or cervical abnormalities. Currently, researchers are planning a Phase III trial which will evaluate the effectiveness of Carraguard. (Carraguard is a gel derived from seaweed that prevents infection of appropriate target cells by HIV and other STIs.) In addition, HPTN has initiated several Phase I trials to study the safety and acceptability of other candidate microbicides and will be conducting a Phase II/IIb trial of two other promising microbicide candidates for vaginal use.
Scientists are no longer studying nonoxynol-9 (N9) as a potential microbicide due to safety concerns and the potential for increased risk of HIV infection as reported at the 13th International Conference on AIDS in Durban, South Africa, in July 2000.

Transmission of HIV to Women

In the United States, most women are infected with HIV during sex with an HIV-infected man or while using HIV-contaminated syringes for the injection of drugs such as heroin, cocaine, and amphetamines. Of the new HIV infections among women in the United States, in 2002, the CDC reported 42 percent were attributed to heterosexual contact and 21 percent to injection drug use.
In the United States, studies have shown that during unprotected heterosexual intercourse with an HIV-infected partner, women have a greater risk of becoming infected than uninfected men who have heterosexual intercourse with an HIV-infected woman. In other parts of the world, however, this is not necessarily true. In Uganda, for example, one study demonstrated that the risk of HIV transmission from woman to man was the same as from man to woman. This difference may be due to the lack of circumcision in Ugandan men.
Studies in both the United States and abroad have demonstrated that STIs, particularly infections that cause ulcerations of the vagina (for example, genital herpes, syphilis, and chancroid), greatly increase a woman's risk of becoming infected with HIV. NIAID-sponsored cohort studies in the United States have also found a number of other factors to be associated with an increased risk of heterosexual HIV transmission, including alcohol use, history of childhood sexual abuse, current domestic abuse, and use of crack/cocaine.
Consistent and correct use of male latex condoms greatly reduces the risk of becoming infected with HIV. In studies of heterosexual couples, in which one individual was HIV-positive and the other uninfected and regular condom use was reported, the rate of HIV transmission was extremely low.
Studies using antiretroviral drugs to try to prevent transmission will be starting soon in the United States and internationally. HPTN Trial 052, which will be conducted in the United States and five other countries, will study approximately 1750 serodiscordant couples with CD4 counts above 300 cells. The trial will determine whether HAART, when given to the infected partner along with prevention counseling and interventions like condoms, prevents HIV transmission to the uninfected partner better than prevention counseling and prevention services alone. Another trial using an antiretroviral drug (tenofovir) to try to prevent HIV transmission in HIV negative sex workers in Cambodia will begin soon.

Mother-to-Child Transmission (MTCT) of HIV
In the United States, approximately 25 percent of pregnant HIV-infected women who do not receive AZT or a combination of antiretroviral therapies pass on the virus to their babies. If women do receive a combination of antiretroviral therapies during pregnancy, however, the risk of HIV transmission to the newborn drops below 2 percent.
The risk of MTCT is significantly increased if the mother has advanced HIV disease, high amounts of HIV in her bloodstream, or fewer-than-normal amounts of the CD4+ T cells.
Other factors that may increase the risk include
• Drug use, such as heroin or crack/cocaine
• Severe inflammation of fetal membranes
• A prolonged period between membrane rupture and delivery
One NIAID-sponsored study found that HIV-infected women who gave birth more than 4 hours after rupture of the fetal membranes were nearly twice as likely to transmit HIV to their babies, as compared to women who delivered within 4 hours of membrane rupture. In the same study, HIV-infected women who used heroin or crack/cocaine during pregnancy were also twice as likely to transmit HIV to their babies as compared to HIV-infected women who did not use drugs.
Most MTCT, an estimated 50 to 70 percent, probably occurs late in pregnancy or during birth. Although the exact ways the virus is transmitted are unknown, scientists think it may happen when the mother's blood enters fetal circulation or by mucosal exposure to the virus during labor and delivery.
Research is underway to identify the mechanisms of MTCT and to develop interventions to reduce it. Notably, NIAID-funded investigators have identified regimens that reduce MTCT. The first regimen to prevent MTCT was identified in a landmark study conducted in 1994 by the PACTG. A specific regimen of AZT given to an HIV-infected woman during pregnancy and to her baby after birth was shown to reduce mother-to-child HIV transmission by two-thirds.
In another NIAID-sponsored study (HIVNET 012) in Uganda, researchers identified a highly effective and safe drug regimen for preventing transmission of HIV from an infected mother to her newborn that is more affordable and practical than any other course of therapy examined to date. The study demonstrated that a single oral dose of the antiretroviral drug, nevirapine, given to an HIV-infected woman in labor and another dose given to her baby within 3 days of birth reduces the transmission rate by about half compared with a course of AZT given only during labor and delivery. Additional data from this study demonstrated the continued benefit and safety of nevirapine in reducing MTCT up to 18 months, even in a breastfeeding population. This study suggests that women in the United States who are identified as HIV-infected very late in pregnancy or at the time of labor and delivery could lower the rates of HIV transmission to their babies by following a nevirapine-containing regimen.
Data from HIVNET 012 also showed that resistance to nevirapine was present in approximately 19 percent of women 6 to 8 weeks after the single dose of nevirapine. After 12 to 24 months, there was no nevirapine resistance detectable in these women using standard methods of HIV resistance testing. Nevertheless, these data are of concern because preliminary data from a small, uncontrolled trial presented at the 2004 Retrovirus Conference in San Francisco by Jourdain et al. showed that women who had received previous single dose nevirapine had poorer virologic outcome when treated with HAART than women who had never received nevirapine.
Additionally, data from an AACTG study showed that subjects who had prior nevirapine, efavirenz, or delaviradine treatment (the anti-HIV drug class abbreviated "NNRTI") had poorer virologic outcomes than those who were NNRTI naïve. The conclusion was that low level, previously unidentified drug resistance can lead to future treatment failure. Given these data, researchers are planning several randomized clinical trials to assess the impact of prior single dose nevirapine on treatment outcomes in the mother, as well the infant, and to assess various strategies to prevent the emergence of drug resistance after single-dose nevirapine used for MTCT.
HIV may also be transmitted from a nursing mother to her child. A series of studies have determined that breastfeeding increases the risk of HIV transmission by about 14 percent. Currently, the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommends that HIV-positive women be educated and counseled so they can make an informed decision about how to best feed their children. Research is underway in areas of the world where the benefits of breastfeeding outweigh the risks to identify effective strategies for reducing the risk of transmission through breastfeeding. This includes early weaning strategies, as well as evaluating drugs or vaccines to reduce the risk of transmission from breastfeeding.
Studies are also underway or planned to determine if antiretroviral drugs given to the uninfected infant or to the infected, breast-feeding mother will prevent HIV transmission to the infant. An example is HPTN 046, which will evaluate the effects of nevirapine on uninfected infants born from HIV infected mothers who are breastfeeding.

Women and HIV: Signs & Symptoms

Many manifestations of HIV disease are similar in men and women. Both men and women with HIV may have non-specific symptoms even early in disease, including low-grade fevers, night sweats, fatigue, and weight loss. Anti-HIV therapies, as well as treatments for other infections associated with HIV, appear to be similarly effective in men and women. Other conditions, however, occur in different frequencies in men and women. HIV-infected men, for instance, are eight times more likely than HIV-infected women to develop a skin cancer known as Kaposi's sarcoma. In some studies, women had higher rates of herpes simplex infections than men.
Data from several studies conducted by CPCRA found that HIV-infected women were also more likely than HIV-infected men to develop bacterial pneumonia. This finding may be explained by factors such as a delay in seeking care among HIV-infected women as compared to men, and/or less access to anti-HIV therapies or preventive therapies for Pneumocystis carinii pneumonia, or PCP.

Woman-Specific Symptoms of HIV Infection
Women also experience HIV-associated gynecologic problems, many of which occur in uninfected women but with less frequency or severity.
Vaginal yeast infections, common and easily treated in most women, often are particularly persistent and difficult to treat in HIV-infected women. Data from WIHS suggest that these infections are considerably more frequent in HIV-infected women. Health care providers commonly use a drug called fluconazole to treat yeast infections. A CPCRA study demonstrated that weekly doses of fluconazole can also safely prevent oropharyngeal and vaginal, but not esophageal yeast infections, without resulting in resistance to the drug.
Other vaginal infections may occur more frequently and with greater severity in HIV-infected women, including bacterial vaginosis and common STIs such as gonorrhea, chlamydia, and trichomoniasis.
Severe herpes simplex virus ulcerations, which are sometimes unresponsive to therapy with the standard drug acyclovir, can severely compromise a woman's quality of life.
Idiopathic genital ulcers, with no evidence of an infectious organism or cancerous cells in the lesion, are a unique manifestation of HIV infection. These ulcers, for which there is no proven treatment, are sometimes confused with those caused by herpes simplex virus.
Human papillomavirus (HPV) infections, which cause genital warts and can lead to cervical cancer, occur more frequently in HIV-infected women. A precancerous condition associated with HPV, called cervical dysplasia, is also more common and more severe in HIV-infected women and more apt to recur after treatment.
Pelvic inflammatory disease (PID) appears to be more common and more aggressive in HIV-infected women than in uninfected women. PID may become a chronic and relapsing condition as a woman's immune system deteriorates.
Menstrual irregularities frequently are reported by HIV-infected women and are being actively studied by NIAID-supported scientists. Although menstrual irregularities were equally common in HIV-infected women and at-risk HIV-negative women in a WIHS survey, women with CD4+ T-cell counts below 50 per cubic millimeter (mm3) of blood were more likely to report no periods than were uninfected women, or HIV-infected women with higher CD4+ T-cell counts.

GYNECOLOGIC SCREENING
CDC currently recommends that HIV-positive women have a complete gynecologic evaluation, including a Pap smear, as part of their initial HIV evaluations, or upon entry to prenatal care, and another Pap smear 6 months later. If both smears are negative, annual screening is recommended thereafter in asymptomatic women. The agency also recommends more frequent screenings-every 6 months-for women with symptomatic HIV infection, prior abnormal Pap smears, or signs of HPV infection.

EARLY DIAGNOSIS
Some women in the United States have poor access to health care. In addition, women may not think they are at risk for HIV infection. They may not heed symptoms that could serve as warning signals of HIV infection, such as recurrent yeast infections. PID and the other symptoms discussed above should signal health care providers to offer women HIV testing with counseling.
Early diagnosis of HIV infection allows women to take full advantage of antiretroviral treatments and preventive medicines for opportunistic infections when their health care providers think it is appropriate. Both appropriate therapy and preventive drugs can forestall the development of AIDS-related symptoms and prolong life in HIV-infected women as well as men. Early diagnosis also allows women to make informed reproductive choices. Health care providers should be ,,,,, to early signs of HIV infection in women. In addition, all women should consider HIV testing if they have engaged in behaviors that put them at risk of infection.

SURVIVAL AMONG HIV-INFECTED WOMEN
Women whose HIV infections are detected early and receive appropriate treatment survive as long as HIV-infected men. Although several studies have shown HIV-infected women to have shorter survival times than men, this may be because women are less likely than men to be diagnosed early.
In an analysis of several studies involving more than 4,500 people with HIV infection, women were 33 percent more likely than men to die within the study period. The investigators could not definitively identify the reasons for excess mortality among women in this study, but they speculated that poorer access to or use of health care resources among HIV-infected women as compared to men, domestic violence, homelessness, and lack of social supports may have been important factors

EXPOSURE AND TRANSMISSION
Most HIV-infected adolescents and young adults are exposed to the virus through sexual intercourse. Recent HIV surveillance data suggest that the majority of HIV-infected adolescent and young adult males are infected through sex with men. Only a small percentage of males appear to be exposed by injection drug use and/or heterosexual contact. The same data also suggest that adolescent and young adult females infected with HIV were exposed through heterosexual contact and a very small percentage through injection drug use.
Approximately 25 percent of cases of sexually transmitted infections (STIs) reported in the United States each year are among teenagers. This is particularly significant because the risk of HIV transmission increases substantially if either partner is infected with an STI. Discharge of pus and mucus as a result of STIs such as gonorrhea or chlamydia infection also increase the risk of HIV transmission three- to five-fold. Likewise, STI-induced ulcers from syphilis or genital herpes increase the risk of HIV transmission nine-fold.

TREATMENT
Adolescents and young adults tend to think they are invincible, and therefore, deny any risk. This belief may cause them to engage in risky behavior, delay HIV testing, and if they test positive, delay or refuse treatment. Doctors report that many young people, when they learn they are HIV-positive, take several months to accept their diagnosis and return for treatment. Health care providers may be able to help these adolescents and young adults understand their situation during visits by
• Ensuring confidentiality
• Explaining the information clearly
• Eliciting questions
• Emphasizing the success of newly available treatments
The U.S. Department of Health and Human Services (DHHS) has developed ,,,,,,,,s that address the standard of care for the treatment of HIV, including information about how to treat HIV in adolescents.
According to the Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, adolescents exposed to HIV sexually or via injection drug use appear to follow a clinical course that is more similar to HIV disease in adults than in children. Most adolescents with sexually acquired HIV are in a relatively early stage of infection and are ideal candidates for early intervention that includes education and counseling, identifying high-risk behaviors, and recommended therapies and behavioral changes.
Adolescents who were infected at birth or via blood products as young children follow a unique clinical course that may differ from that of other adolescents and adults. Health care providers should refer to the treatment guidelines for detailed information about the treatment of HIV-infected adolescents.

CLINICAL TRIALS
The National Institute of Allergy and Infectious Diseases (NIAID), supports clinical trials at many clinics and medical centers throughout the United States. These studies help evaluate promising therapies to
• Prevent HIV infection
• Discover new therapies to improve control of viral replication in patients with HIV/AIDS
• Prevent and treat co-infections and cancers associated with AIDS
• Prevent and treat complications of HIV therapies
• Reconstitute HIV-damaged immune systems
Recruiting adolescents and young adults into clinical trials is important to ensure that research results will be applicable to therapy for that age group. Most clinical trials are open to adolescents and young adults, but in reality very few enroll. Of the nearly 11,000 participants in studies conducted by the NIAID-supported Adult and Pediatric AIDS Clinical Trials Groups in Fiscal Year 2003, only 4.1 percent of the participants were adolescents (age 13-19). To encourage participation by more adolescents and young adults, NIAID has identified adolescent treatment as an area of emphasis for the Pediatric AIDS Clinical Trials Group (PACTG). Funded by NIAID and the National Institute of Child Health and Human Development (NICHD), the PACTG's adolescent treatment research agenda focuses on
• Expanding and enhancing adolescent research at all PACTG sites
• Engaging youth in treatment research opportunities
• Studying the effects of treatment on acute and early infection
• Restoring immune function
• Strengthening and augmenting long-term follow-up studies of safety and clinical effectiveness of antiretroviral therapies
• Promoting collaborations to assist in prevention research

HIV Infection in Infants and Children

OVERVIEW
The National Institute of Allergy and Infectious Diseases (NIAID) has a lead role in research devoted to children infected with HIV (human immunodeficiency virus), the virus that causes AIDS (acquired immunodeficiency syndrome). NIAID-supported researchers are developing and refining treatments to prolong the survival and improve the quality of life of HIV-infected infants and children through the Pediatric AIDS Clinical Trials Group (PACTG). The PACTG is a nationwide clinical trials network jointly sponsored by NIAID and the National Institute of Child Health and Human Development (NICHD). NIAID also supports research on ways to prevent mother-to-child transmission (MTCT) of HIV through the PACTG and its HIV Prevention Trials Network (HPTN), a global clinical trials network designed to test promising nonvaccine strategies to prevent the spread of HIV/AIDS.
In this era of antiretroviral therapy, epidemiologic studies such as NIAID's Women and Infant's Transmission Study (WITS) are examining risk factors for transmission as well as the course of HIV disease in pregnant women and their babies. Researchers have helped illuminate the mechanisms of HIV transmission, the distinct features of pediatric HIV infection, and how the course of disease and the usefulness of therapies can differ in children and adults.

A GLOBAL PROBLEM
According to UNAIDS (The Joint United Nations Programme on HIV/AIDS) at the end of 2003, an estimated 2.5 million children worldwide under age 15 were living with HIV/AIDS. Approximately 500,000 children under 15 had died from the virus or associated causes in that year alone. As HIV infection rates rise in the general population, new infections are increasingly concentrating in younger age groups.
December 2003 UNAIDS/World Health Organization (WHO) worldwide statistics show
• 700,000 children under age 15 were newly infected with HIV
• Thirteen percent of all new HIV infections were in children under age 15
• Three million children in sub-Saharan Africa, the region with the highest number of cases, are living with HIV
More than 95 percent of all HIV-infected people now live in developing countries, which have also suffered 95 percent of all deaths from AIDS. In those countries with the highest prevalence, UNAIDS predicts that, between 2000 and 2020, 68 million people will die prematurely as a result of AIDS. In seven sub-Saharan African countries, mortality due to HIV/AIDS in children under age five has increased by 20 to 40 percent. Life expectancy for a child born in Botswana, the country with the highest HIV prevalence in the world, has dropped below 40 years-a level not seen in that country since before 1950.
The United States has a relatively small percentage of the world's children living with HIV/AIDS. From the beginning of the epidemic through the end of 2002, 9,300 American children under age 13 had been reported to the Centers for Disease Control and Prevention (CDC) as living with HIV/AIDS. The vast majority of HIV-infected children acquire the virus from their mothers before or during birth or through breast feeding. Because of the widespread use of AZT and other highly active antiretroviral therapy (HAART) in HIV-infected pregnant women in the United States, only 92 new cases of pediatric AIDS were reported in 2002. More than three times that number are infected with HIV but have not yet developed AIDS.
• The U.S. city with the highest rate of pediatric AIDS through 2002 was New York City, followed by Miami, FL, and Washington, DC.
• The disease disproportionately affects children in minority groups, especially African Americans. Out of 9,300 cases in children under 13 reported to the CDC through December 2002, 59 percent were black/non-Hispanic, 23 percent were Hispanic, 17 percent were white/non-Hispanic, and less than 1 percent were in other minority groups.

New anti-HIV drug therapies and promotion of voluntary testing continue to positively effect the death rate. CDC reported a drop of 68 percent from 1998 to 2002 in the estimated number of children who died from AIDS.
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HIV Infection in Infants and Children: Tranmission

TRANSMISSION
Almost all HIV-infected children acquire the virus from their mothers before or during birth or through breastfeeding. In the United States, approximately 25 percent of pregnant HIV-infected women not receiving AZT therapy have passed on the virus to their babies. The rate is significantly higher in developing countries.
Prior to 1985 when screening of the nation's blood supply for HIV began, some children as well as adults were infected through transfusions with blood or blood products contaminated with HIV. A small number of children also have been infected through sexual or physical abuse by HIV-infected adults.
PREGNANCY AND BIRTH
Most MTCT, estimated to cause more than 90 percent of infections worldwide in infants and children, probably occurs late in pregnancy or during birth. Although the precise mechanisms are unknown, scientists think HIV may be transmitted when maternal blood enters the fetal circulation or by mucosal exposure to virus during labor and delivery. The role of the placenta in maternal-fetal transmission is unclear and the focus of ongoing research.
The risk of MTCT is significantly increased if the mother has advanced HIV disease, increased levels of HIV in her bloodstream, or fewer numbers of the immune system cells-CD4+ T cells-that are the main targets of HIV.
Other factors that may increase the risk are maternal drug use, severe inflammation of fetal membranes, or a prolonged period between membrane rupture and delivery. A study sponsored by NIAID and others found that HIV-infected women who gave birth more than 4 hours after the rupture of the fetal membranes were nearly twice as likely to transmit HIV to their infants, as compared to women who delivered within 4 hours of membrane rupture.
BREASTFEEDING
HIV also may be transmitted from a nursing mother to her infant. Studies have suggested that breastfeeding introduces an additional risk of HIV transmission of approximately 10 to 14 percent among women with chronic HIV infection. In developing countries, an estimated one-third to one-half of all HIV infections are transmitted through breastfeeding.
WHO recommends that all HIV-infected women be advised about both the risks and benefits of breastfeeding for their infants so they can make informed decisions. In countries where safe alternatives to breastfeeding are readily available and economically feasible, this alternative should be encouraged. In general, in developing countries where safe alternatives to breastfeeding are not readily available, the benefits of breastfeeding in terms of decreased illness and death due to other infectious diseases greatly outweigh the potential risk of HIV transmission.
PREVENTING MOTHER-TO-CHILD TRANSMISSION
In 1994, a landmark study conducted by the PACTG demonstrated that AZT, given to HIV-infected women who had very little or no prior antiretroviral therapy and CD4+ T-cell counts above 200/mm3, reduced the risk of MTCT by two-thirds, from 25 percent to 8 percent. In the study, AZT therapy was initiated in the second or third trimester and continued during labor, and infants were treated for 6 weeks following birth. AZT produced no serious side effects in mothers or infants. Long-term follow up of the infants and mothers is ongoing.
A few years later, another PACTG study found that the risk of transmitting HIV from an HIV-positive mother to her newborn infant could be reduced to 1.5 percent in those women who received antiretroviral treatment and appropriate medical and obstetrical care during pregnancy.
Combination therapies have been shown to be beneficial in treating HIV-infected adults, and current guidelines have been designed accordingly. In HIV-infected pregnant women, the safety and pharmacology of these potent drug combinations need to be better understood, and NIAID is conducting studies in this area.
The AZT regimen is not available in much of the world because of its high cost and logistical requirements. The cost of a short-course AZT regimen is substantially lower, but is still prohibitive in many countries. International agencies are studying whether there may be innovative ways to provide AZT at lower cost, for example, through reductions in drug prices to developing countries or partnerships with industry. As a result, NIAID continues to evaluate other strategies that may be simpler and less costly to prevent MTCT in various settings. In September 1999, one such study demonstrated that short-course therapy with nevirapine lowered the risk of HIV-1 transmission during the first 14 to16 weeks of life by nearly 50 percent compared to AZT in a breastfeeding population. As a follow up, NIAID released a final report on additional data showing that the results of nevirapine were sustained after 18 months. These findings have significant implications because this simple, inexpensive regimen offers a potential cost-effective alternative for decreasing MTCT in developing countries.
In addition, in April 1999 the International Perinatal HIV Group reported that elective caesarian section delivery can help reduce vertical transmission of HIV, though it is not without risk to certain women. When AZT treatment is combined with elective caesarian delivery, a transmission rate of 2 percent has been reported.
Because a significant amount of MTCT occurs around the time of birth, and the risk of maternal-fetal transmission depends, in part, on the amount of HIV in the mother's blood, it may be possible to reduce transmission using drug therapy only around the time of birth. NIAID has planned other studies that will assess the effectiveness of this approach as well as the role of new antiretrovirals, microbicides and other innovative strategies in reducing the risk of MTCT of HIV.
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HIV Infection in Infants and Children: Diagnois and Symptoms

DIAGNOSIS
HIV infection is often difficult to diagnose in very young children. Infected babies, especially in the first few months of life, often appear normal and may show no telltale signs allowing for a definitive diagnosis of HIV infection. Moreover, all children born to infected mothers have antibodies to HIV, made by the mother's immune system, that cross the placenta to the baby's bloodstream before birth and persist for up to 18 months. Because these maternal antibodies reflect the mother's but not the infant's infection status, the test for HIV infection is not useful in newborns or young infants.
In recent years, investigators have demonstrated the utility of highly accurate blood tests in diagnosing HIV infection in children 6 months of age and younger. One laboratory technique, called polymerase chain reaction (PCR), can detect minute quantities of the virus in an infant's blood. Another procedure allows physicians to culture a sample of an infant's blood and test it for the presence of HIV.
Currently, PCR assays or HIV culture techniques can identify at birth about one-third of infants who finally and ultimately prove to be HIV infected. With these techniques, approximately 90 percent of HIV-infected infants are identifiable by 2 months of age, and 95 percent by 3 months of age. One innovative new approach to both RNA and DNA PCR testing uses dried blood spot specimens, which should make it much simpler to gather and store specimens in field settings.
PROGRESSION OF HIV DISEASE IN CHILDREN
Researchers have observed two general patterns of illness in HIV-infected children. About 20 percent of children develop serious disease in the first year of life; most of these children die by age 4. The remaining 80 percent of infected children have a slower rate of disease progression, many not developing the most serious symptoms of AIDS until school entry or even adolescence. A report from a large European registry of HIV-infected children indicated that half of the children with perinatally acquired HIV disease were alive at age nine. Another study of 42 perinatally HIV-infected children, who survived beyond 9 years of age, found about one-quarter of the children to be asymptomatic with relatively intact immune systems.
The factors responsible for the wide variation observed in the rate of disease progression in HIV-infected children are a major focus of the NIAID pediatric AIDS research effort. WITS is a multisite perinatal HIV study. It has found that maternal factors, including Vitamin A level and CD4+ T-cell counts during pregnancy, as well as infant viral load and CD4+ T-cell counts in the first several months of life, can help identify those infants at risk for rapid disease progression who may benefit from early aggressive therapy.
SIGNS AND SYMPTOMS
Many children with HIV infection do not gain weight or grow normally. HIV-infected children frequently are slow to reach important milestones in motor skills and mental development such as crawling, walking, and talking. As the disease progresses, many children develop neurologic problems such as difficulty walking, poor school performance, seizures, and other symptoms of HIV encephalopathy (a brain disorder).
Like adults with HIV infection, children with HIV develop life-threatening opportunistic infections (OIs), although the incidence of various OIs differs in adults and children.
• Toxoplasmosis (a parasitic disease) is seen less frequently in HIV-infected children than in HIV-infected adults, while serious bacterial infections occur more commonly in children than in adults.
• Pneumocystis carinii pneumonia (PCP) is the leading cause of death in HIV-infected children with AIDS. PCP, as well as cytomegalovirus (CMV) disease, usually are primary infections in children, whereas in adults these diseases result from the reactivation of latent infections.
• A lung disease called lymphocytic interstitial pneumonitis (LIP), rarely seen in adults, occurs more frequently in HIV-infected children. This condition, like PCP, can make breathing progressively more difficult and often results in hospitalization.
• Severe candidiasis, a yeast infection that can cause unrelenting diaper rash and infections in the mouth and throat that make eating difficult, is found frequently in HIV-infected children.
• As children with HIV become sicker, they may suffer from chronic diarrhea due to opportunistic pathogens.
Children with HIV suffer the usual childhood infections more frequently and more severely than uninfected children. These infections can cause seizures, fever, pneumonia, recurrent colds, diarrhea, dehydration, and other problems that often result in extended hospital stays and nutritional problems.
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HIV Infection in Infants and Children: Treatment

While the basic principles that guide treatment of pediatric HIV infection are the same as for an HIV-infected adult, there are a number of unique scientific and medical concerns that are important to consider in treating children with HIV infection. These range from differences in age-related issues such as CD4+ T-cell counts and drug ,,,,bolism to requirements for special formulations and treatment regimens that are appropriate for infants through adolescents. As in adults, treating HIV-infected children today is a complex task of using potent combinations of antiretroviral agents to maximally suppress viral replication. NIAID investigators are defining the best treatments for pediatric patients.
NIAID-supported researchers are focusing not only on the development of new antiretroviral products but also on the critical question of how to best use the treatments that are currently available, especially in resource-poor nations. Treatment strategy questions should be designed to identify, for example, the best initial therapy, when failing regimens should be modified, and strategies to address the antiretroviral needs of children with advanced disease. Another high priority is the long-term assessment of these strategies to determine sustained antiretroviral benefits as well as to monitor for potential adverse consequences of treatment.
PROBLEMS IN FAMILIES
A mother and child with HIV usually are not the only family members with the disease. Often, the mother's sexual partner is infected, and other children in the family may be infected as well. Frequently, a parent with AIDS does not survive to care for his or her HIV-infected child.
In the countries hardest hit by the AIDS epidemic, some 14 million children under 15 around the world have been orphaned by AIDS-80 percent of them (11 million) in sub-Saharan Africa alone. The rate is expected to increase. One in three of these orphans is under age five. Communities and extended families are struggling with and often overwhelmed by the vast number of children orphaned by AIDS. Many orphans and other children from families devastated by AIDS face multiple risks, such as forced relocation, violence, living on the streets, drug use, and even commercial sex. Other children suffer because sexuality education and services are not available to them or not effectively communicated to them. Living in a country undergoing political turmoil or can also raise the risk of a child becoming HIV-infected.
In the United States, most children living with HIV/AIDS live in inner cities, where poverty, illicit drug use, poor housing, and limited access to and use of medical care and social services add to the challenges of HIV disease.
One encouraging note is, according to UNAIDS, that where information, training, and services to help prevent HIV infection are made available and affordable, young people are more likely to make use of them than their elders.
Management of the complex medical and social problems of families affected by HIV requires a multidisciplinary case management team, integrating medical, social, mental health, and educational services. NIAID provides special funding to many of its clinical research sites to provide for services, such as transportation, day care, and the expertise of social workers, crucial to families devastated by HIV.

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