لمن يحب المساعده

[فتاة النخيل]

سلام

بصراحه انا معي موضوع طلبته هنا بالمنتدىوالحمد لله دلوني عليه جزاهم الله خير وقد كتب من قبل فيه ولكني تمنيت لو انه كان باللغه الانجليزيه لان الموضوع عباره عن مرض ونحنا دايما نتعامل مع الامراض باللغه الانجليزيه تبعا للتعليم للطب وبالتالي اطلب من منيجد عنده القدره على ترجمته ان يساعدني في الترجمه لاني تعبت في ترجمته نظرا لاني اللغه عندي ضعيفه شويه فياريت يكون هناك احد جدير بطلبي ...
وياريت اذا قدرتوا بأسرع وقت ممكن بلييييييز ...
والموضوع هو عن مرض الايدز اعاذنا الله واياكم منه وهو موجود في الرابط التالي :

http://www.montada.com/showthread.ph...22#post3145022

ولكم خالص الشكر والتقدير

[HIROSHI_11]

مرحبا

أهلين أختي كيف الحال؟ عساج بخيرة.

أنا أقدر اساعدج لكن ظروفي ما تسمح إني اترجم المعلومات . فاذا حبيتي انا ممكن اجيبلج معلومات عن مرض الأيدز بالإنجليزي غير عن المعلومات الي عطوج . اذا موافقة خبريني. نسيت اقول ان المعلومات حوالي 26 :shock22: صفحة على الميكروسوفت وورد . واعتذر عن الرد المتأخر.



مع السلامة

[فتاة النخيل]

السلام عليكم

مشكور اخوي على مرورك ومساعدتك لي
اما بالنسبه لطلبي فأنا اقول لك لو سمحت اذا معك الموضوع نفسه ( الايدز ) بالانجليزي فياريت ترسله لي بأسرع وقت ممكن واللي يسلمك المهم يكون الموضوع نفسه وبالانجليزي
لاني ترى والله محتاجة له جدا جدا
ومهما يكن عدد صفحاته ابيه

والسلام عليكم

[HIROSHI_11]

مرااحب

أهلين. هذه هي المعلومات إلي طلبتيها . وأعتذر عن التأخير . وفي كم صورة في الملفات المرفقة.



:shock22: :shock22:

INTRODUCTION

Acquired Immune Deficiency Syndrome (AIDS), a clinical syndrome (a group of various illnesses that together characterize a disease) resulting from damage to the immune system caused by infection with the human immunodeficiency virus (HIV).



AIDS Virus The Human Immunodeficiency Virus (HIV), which causes acquired immune deficiency syndrome (AIDS), principally attacks T-4 lymphocytes, a vital part of the human immune system. As a result, the body’s ability to resist opportunistic viral, bacterial, fungal, protozoal, and other infection is greatly weakened. Pneumocystis carinii pneumonia is the leading cause of death among people with HIV infection, but the incidence of certain types of cancers such as B-cell lymphomas and Kaposi’s sarcoma is also increased. Neurological complications and dramatic weight loss, or wasting, are characteristic of AIDS, which is endstage HIV disease. HIV is transmitted sexually; through contact with contaminated blood, tissue, or needles; and from mother to child during birth or breast-feeding. Full-blown symptoms of AIDS may not develop for more than 10 years after infection.Photo Researchers, Inc./Luc Montagnier/Institut Pasteur/CNRI/Science Source



In HIV-infected individuals, there is a gradual loss of immune cells (called CD4+ T-lymphocytes) and immune function. The mechanisms by which HIV causes this immune deficiency are still not completely understood, although direct infection of CD4+ T-lymphocytes by HIV certainly plays a role. The loss of immune function, if untreated, results eventually in the development of opportunistic diseases caused by common infections that do not present a threat to healthy individuals, including fungal, bacterial, protozoal, and viral diseases, as well as by malignancies that appear to be associated with immune dysregulation. In the absence of treatment, it generally takes six to ten years from the point of infection to develop AIDS, although the rate of disease progression may vary substantially from person to person.



Luc Montagnier In 1983, while working at the Pasteur Institute in Paris, scientists led by Luc Montagnier became one of three groups to simultaneously discover the Human Immunodeficiency Virus. The other two groups included one at the National Cancer Institute, Maryland, led by Robert Gallo, and a group at the University of California, San Francisco, headed by Jay Levy. Montagnier's group had made their discovery when they isolated what appeared to be a new human retrovirus from the lymph node of a man at risk of developing AIDS. Luc Montagnier is here pictured in 1991.Sygma/J. Andanson



In the early 1980s deaths by opportunistic infections, previously observed mainly in transplant recipients receiving immunosuppressive therapy, were recognized in otherwise healthy homosexual men. In 1983, Luc Montagnier and scientists at the Pasteur Institute in Paris isolated what appeared to be a new human retrovirus from the lymph node of a man at risk of developing AIDS. Almost simultaneously, both Robert Gallo’s group at the National Cancer Institute (NCI), and a group headed by Jay Levy at the University of California, San Francisco, isolated a retrovirus from AIDS patients and from people who had had sexual contact with AIDS patients. All three groups had isolated what is now known as HIV—the aetiological (causative) agent of AIDS.



II DETECTION AND DIAGNOSIS



With the identification of HIV in 1983 came the opportunity to develop a method of specific detection. The screening tests now in widespread use by blood banks, plasma centres, reference laboratories, private clinics, and health departments analyse a sample of blood for the presence of antibodies produced by the immune system in response to infection with HIV. Separate serological tests were developed to detect HIV-1 and HIV-2, owing to the major differences in the protein components of these two related viruses. There are also different sub-types (or "clades") of HIV-1 and HIV-2, reflecting the different evolutionary paths that the viruses have taken in specific geographical locations. As new sub-types of HIV are identified from around the world, they too will need to be evaluated for detection by these tests.



There is a brief “window period” (normally four to eight weeks) after exposure to HIV during which standard screening tests are unable to detect the presence of HIV because the immune system has not had enough time to make antibodies against HIV. During this period, other methods that use amplification techniques (such as polymerase chain reaction) to detect the genetic material of the virus itself, rather than antibodies against it, may be able to determine whether an individual is infected with HIV.



A person who receives a positive test result for HIV infection is often described as HIV-positive. Being HIV-positive does not necessarily imply that a person also has AIDS. A person can be infected with HIV for a long period—greater than ten years—without developing any of the clinical illnesses that constitute a diagnosis of AIDS.



The Centers for Disease Control and Prevention in Atlanta, Georgia, established an authoritative definition for the diagnosis of AIDS: in an HIV-positive individual, the CD4+ cell count must be below 200 cells per cu mm of blood, or there must be the clinical appearance of a specific opportunistic condition that is considered AIDS-defining, from a long list that includes Pneumocystis carinii pneumonia (PCP), oesophageal candidiasis (thrush), pulmonary tuberculosis, and invasive cervical carcinoma. In Europe, however, a CD4+ cell count below 200 is not in itself grounds for the diagnosis of AIDS; HIV-positive people must have an AIDS-defining opportunistic illness to be diagnosed with AIDS.



III NATURE OF THE DISEASE



A Clinical Progression of AIDS



A1 Measuring Progression



The progression from the point of HIV infection to the occurrence of one (or more) of the clinical diseases that define AIDS may take six to ten years or longer. The progression to disease in HIV-infected individuals can be monitored using surrogate markers (laboratory data that correlate with disease progression), or clinical end points (illnesses that can occur after a specific degree of immunosuppression has been reached). Surrogate markers for the various stages of HIV disease include the progressive loss of CD4+ T-lymphocytes (CD4+ T-cells), the major white blood cells lost through HIV infection. In general, the lower the patient's CD4+ T-cell count, the more advanced is the degree of immunosuppression. The amount of HIV circulating in the blood is a second surrogate marker. Using sensitive detection techniques, the quantity of HIV in the blood of an untreated individual correlates with the clinical stage of the disease and predicts the rate of disease progression.



A2 Acute Retroviral Syndrome



A well-recognized progression of disease occurs in untreated HIV-infected individuals. Within one to three weeks after infection with HIV, many (but not all) individuals experience non-specific flu-like symptoms that may include fever, headache, skin rash, tender lymph nodes, and malaise, lasting approximately one to two weeks. During this phase, termed acute retroviral syndrome or primary HIV infection, HIV reproduces itself to very high levels, circulates through the blood, and establishes infections in tissues throughout the body, especially in the lymph nodes. Patients’ CD4+ cell counts fall briefly but return to near-normal levels as the immune system recognizes the infection and mounts an immune response that reduces HIV replication, albeit incompletely.



A3 Asymptomatic Phase



Individuals then enter a prolonged asymptomatic phase that can last ten years or more. During this period, infected individuals usually remain in good health, with levels of CD4+ cells in the low-normal range (750 to 500 cells per cu mm). However, HIV continues to replicate during the asymptomatic phase, causing a progressive destruction of the immune system. Eventually, the immune system declines and patients enter the early symptomatic phase.



A4 Symptomatic Phases



AIDS Prevention Sign, Botswana A road sign in Botswana about acquired immune deficiency syndrome (AIDS) says “AIDS: Your Problem, Control With Condoms”. Africa accounts for more than 60 per cent of adults infected with human immunodeficiency virus (HIV), the cause of AIDS.Photo Researchers, Inc./M.P. Kahl



The early symptomatic phase can last from only a few months to several years and is characterized by rapidly falling levels of CD4+ cells (500 to 200 cells per cu mm) and non-life-threatening opportunistic infections. From this phase, patients undergo more extensive immune destruction and serious illness that characterize the late symptomatic phase. The late phase again can last from only a few months to years and patients may have CD4+ cell counts below 200 along with AIDS-defining opportunistic conditions. A wasting syndrome of progressive weight loss and debilitating fatigue is observed in a large proportion of untreated patients in this stage. The immune system is now in severe failure, with a CD4+ cell count below 50. In the absence of effective anti-HIV therapy, death from life-threatening AIDS-defining opportunistic infections and cancers is likely to occur within one to two years.



B Opportunistic Conditions



Death from AIDS is generally not due to HIV infection itself, but due to opportunistic conditions. These infections and malignancies occur when the immune system can no longer provide protection against agents normally found in the environment. The appearance of any one of more than 20 different opportunistic infections, termed AIDS-defining illnesses, provides the clinical diagnosis of AIDS in HIV-infected individuals.



The most common opportunistic infection seen in AIDS is PCP, caused by a fungus (Pneumocystis carinii), which exists in the airways of all individuals. Bacterial pneumonia (caused by several types of bacteria including Streptococcus and Haemophilus) and tuberculosis (TB: a bacterial respiratory infection caused by Mycobacterium tuberculosis) are also commonly associated with AIDS.



In late-stage AIDS, disseminated infection by Mycobacterium avium intracellulare complex can cause fever, weight loss, anaemia, and diarrhoea. Additional bacterial infections of the gastrointestinal tract (from Salmonella, Campylobacter, Shigella, or other bacteria) commonly cause diarrhoea, weight loss, anorexia (loss of appetite), and fever.



Besides PCP, other fungal infections, or mycoses, are frequently observed in AIDS patients. Oral candidiasis, or thrush (infection of the mouth by the fungus Candida), is seen early in the symptomatic phase in a high proportion of patients. Oesophageal candidiasis (affecting the throat) is a more serious, AIDS-defining illness. Other mycoses include infections with Cryptococcus species, a major cause of meningitis in up to 13 per cent of AIDS patients, and disseminated histoplasmosis, caused by Histoplasma capsulatum, that affects up to 10 per cent of AIDS patients in the south-central United States and South America, but is very rare in the United Kingdom and mainland Europe.



Viral opportunistic infections, especially with members of the herpes virus family, are common in AIDS patients. One herpes family member, cytomegalovirus (CMV), may infect the retina and can result in blindness. Another herpes virus, Epstein-Barr virus, may result in a cancerous transformation of blood cells. Also common are infections with herpes simplex virus types 1 and 2 that result in progressive oral, genital, and perianal lesions.



Neurological problems that may occur among AIDS patients include: HIV encephalopathy (also known as AIDS dementia), caused by direct infection of brain cells by HIV; progressive multifocal leukoencephalopathy, caused by the JC virus; and toxoplasmosis, caused by a protozoal infection, Toxoplasma gondii.



Many AIDS patients develop cancers, the most common being Kaposi’s sarcoma (KS) and B-cell lymphoma. KS is caused by the cancerous transformation of cells in the skin or internal organs, resulting in purple lesions on the skin, lungs, gastrointestinal tract, or elsewhere in the body. A less serious form of KS also occurs among certain non-HIV-infected populations in Africa and the Mediterranean. It is caused by a recently discovered virus, human herpes virus 8 (HHV-8), which appears to be most commonly transmitted in saliva and during sexual contact. KS occurs relatively commonly among HIV-positive homosexual men and Africans but is rare among other HIV-infected people, reflecting the distribution of HHV-8 in different population groups.

[HIROSHI_11]

IV CAUSE OF AIDS



A Global Epidemic More than 40 million people around the world are currently infected with the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS). New HIV infections have levelled off or even declined in most developed countries, but the virus is spreading rapidly through much of the developing world. In some areas of sub-Saharan Africa, one in four adults are carrying the virus.© Microsoft Corporation. All Rights Reserved.





A Human Immunodeficiency Virus (HIV)



The aetiological agent of AIDS is HIV, a human retrovirus. HIV is closely related to viruses that cause similar immunodeficiency diseases in a range of animal species. Its origin in humans is widely accepted to have resulted from cross-species transfer of a simian immunodeficiency virus (SIV) from the chimpanzee, Pan troglodytes troglodytes, in central Africa, probably centuries ago. Changing social mores and urbanization are believed to have provided the conditions necessary for the emergence of HIV as a pandemic during the latter decades of the 20th century.



HIV is an enveloped virus, meaning that the viral genetic material is surrounded by a lipid membrane derived from the host cell. HIV enters susceptible cells by the fusion of its envelope glycoproteins gp120 and gp41 with specific molecules in the lipid membrane of certain cells, allowing the viral genetic material to enter the cell and eventually replicate, leading to cell death. The most important cellular receptor is CD4, a surface molecule important for normal immune interaction, but other co-receptors called CCR5 and CXCR4 are also important. Inherited genetic factors affect the extent to which an individual’s cells express these co-receptors, which in turn may affect their susceptibility to infection with HIV, or their rate of disease progression if they do become infected.



Any human cell that expresses the necessary receptor molecules is a potential target for HIV infection. However, the cells that are most affected during HIV infection are white blood cells that express high levels of the CD4 molecule, and are therefore referred to as “CD4-positive (CD4+) T-cells”. HIV replication in CD4+ T-cells can directly kill them or they may be killed or rendered dysfunctional by indirect means without ever being infected with HIV.



CD4+ T-cells are critical in the normal immune system because they help other types of immune cells recognize and respond to invading organisms. Therefore, as CD4+ T-cells are specifically targeted and lost during HIV infection (a hallmark feature of AIDS), no help is available for immune responses. General immune system failure occurs and permits the opportunistic infections and cancers that characterize the clinical picture of AIDS.



While it is agreed that HIV is the virus that causes AIDS, and that HIV replication can directly kill CD4+ T-cells, the large variation among patients in the time of progression to AIDS indicates that other factors can influence the course of disease. Several inherited genetic factors have been shown to influence an individual's susceptibility to acquiring HIV and, once infected, to HIV-induced immune damage. Other factors that may influence the rate of disease progression remain unclear, but may include the nature of the infected person’s immune response to HIV, and perhaps certain viral co-infections. However, it is very clear that HIV must be present for the development of AIDS.



B Modes of Transmission



HIV can be transmitted by either homosexual or heterosexual contact with an infected person and these routes represent the majority of transmissions. Present in the sexual secretions of both men and women, HIV gains access to the bloodstream of the uninfected partner by infecting cells in mucous membranes or via small abrasions that occur as a consequence of intercourse. HIV is also spread by sharing injecting equipment, most commonly done by those abusing drugs, and this results in a direct exposure to the blood from an infected individual.



HIV transmission through medical transfusions or blood-clotting factors is now extremely rare because of extensive screening of the blood supply. HIV can also be transmitted from an infected mother (either before giving birth, during labour, or through breastfeeding), but only about 30 per cent of babies born to untreated HIV-infected mothers are actually infected, and the use of antiviral medications by the mother and the newborn child can reduce this risk almost to zero.



Although these routes of HIV transmission are well established, public fear still exists concerning the potential for transmission by other means. There is no evidence that HIV can be transmitted through the air or by biting insects. If this were the case, the pattern of HIV infections would be dramatically different from what has been observed and cases of AIDS would be reported more frequently in individuals with no identifiable risk for infection (now only a very small percentage of reported cases).



Although HIV is a very fragile virus and does not survive well when exposed to the environment (for example, drying of HIV-infected fluids rapidly reduces their infectiousness almost to zero), fear also exists for HIV transmission by casual contact in a household, school, workplace, or food-service setting. No documented cases of HIV transmission by casual contact with, or even kissing, an infected individual have been identified. However, practices that increase the likelihood of blood contact, such as sharing toothbrushes or razors, should be avoided.



Public fear has also persisted regarding HIV transmission from infected health-care workers, because of a case of transmission from a dentist to several patients. This now appears to be an extremely rare and isolated case of transmission and, in general, infected health-care workers pose no risk to their patients. There is no risk of HIV transmission while donating blood.



C Epidemiology



Global Distribution of People with HIV/AIDS

Expand



By the end of 2002, 42 million adults and children were estimated to be living with HIV, of whom 5 million were believed to have become infected during 2002. A total of about 25 million people were estimated to have died from AIDS since the start of the pandemic. The epidemiology (incidence and distribution) of AIDS is an evolving picture. Initially in the United States, HIV infection was mainly concentrated in the homosexual community, where widespread transmission occurred because of unprotected anal intercourse, and in haemophiliacs and people receiving other blood products. HIV infection became established among IV drug users, who in turn infected their heterosexual partners. African-American communities in the United States have relatively high rates of HIV infection among both heterosexuals and homosexuals; although they represent only an estimated 12 per cent of the US population, they make up 34 per cent of all US AIDS cases.



C1 Epidemiology in the United States and the United Kingdom



By the end of December 2001, over 807,000 adults and over 9,000 children had been diagnosed with AIDS in the United States, and over 174,000 people had been reported to have HIV infection (but not AIDS) in the 36 areas that have confidential HIV reporting systems. Approximately 40,000 Americans are estimated to be newly infected with HIV each year. Among adults and adolescents, three HIV exposure categories continue to account for nearly all cases of AIDS in the United States: homosexual contact (46 per cent); injection-drug use (25 per cent); and heterosexual contact with a person who is in a high-risk group or has HIV (11 per cent). The vast majority of AIDS cases among children have resulted from mother-to-baby HIV transmission. Thanks to effective screening, HIV transmission by blood products is now rare, constituting 1 per cent of cases during the entire course of the epidemic.



By the end of September 2002, 18,972 cases of AIDS had been reported in the United Kingdom, of whom 14,910 (79 per cent) had died. Including these AIDS cases, a total of 52,666 cases of HIV infection had been reported. Sex between men remains the commonest exposure category, accounting for 54 per cent of all cases of HIV reported to date, although in every year since 1999, a greater proportion of newly detected cases has been attributed to heterosexual contact than to homosexual contact. In the United Kingdom, most cases of HIV infection attributed to sex between men and women reflect exposure to HIV while abroad, especially in Africa.



C2 Epidemiology in the Developing World



AIDS Headlines, 1980s As the number of cases of acquired immune deficiency syndrome (AIDS) in the United States reached epidemic proportions in the 1980s, public concern also grew. With no vaccine yet developed, educating the public about AIDS has been the primary approach to prevention.Photo Researchers, Inc./Van Bucher



On a global scale, AIDS continues a frightful expansion. Over 25 million people are estimated to have died from AIDS worldwide by the end of 2002. At that time, 29.4 million individuals in sub-Saharan Africa were estimated to be living with HIV/AIDS, representing 8.8 per cent of all adults. Of the estimated 5 million people who acquired new HIV infection during 2002, 3.5 million lived in sub-Saharan Africa, and over 75 per cent of the 3.1 million adults and children who died due to AIDS during 2002 also lived in sub-Saharan Africa. In four sub-Saharan African countries, more than 30 per cent of the adult population is now infected: Botswana (38.8 per cent), Lesotho (31 per cent), Swaziland (33.4 per cent), and Zimbabwe (33.7 per cent).



Impact of AIDS on Population Structure This chart shows the dramatic impact that acquired immune deficiency syndrome (AIDS) is predicted to have on the structure of the population of Botswana, a nation badly hit by the AIDS epidemic. By 2020 AIDS will have reduced the number of women of childbearing age in Botswana, and therefore fewer babies will be born. Furthermore, many infants will be infected by their mothers, and will die of AIDS in their childhood. As surviving children reach adulthood, many of them will become infected through sexual intercourse, and will die in their 20s and 30s. Only those who avoid infection will survive to older ages.© Microsoft Corporation. All Rights Reserved.



There are an additional 6 million infected individuals living in South and South East Asia, and 1.5 million in Latin America. Infection rates are currently rising fastest in Eastern Europe and Central Asia, where over one fifth of the estimated 1.2 million HIV-positive people acquired the virus during 2002 alone. There are also rapidly growing epidemics in China, with 1 million HIV-positive people, and in India with 4 million.



V TREATMENT



By the end of 2002, 16 antiretroviral drugs had been approved for use in the treatment of HIV infection. From the late 1980s until the mid-1990s, the available drugs were generally used one at a time in sequence, but their effects were disappointingly short-lived. Greater success has been achieved by using them in combination regimens, which can significantly delay the onset of opportunistic infections and prolong life. Current guidelines for the use of antiretroviral drugs advise that they should be used in combinations of three or more drugs. These potent regimens, known as highly active antiretroviral therapy (HAART) regimens, have had dramatic effects in reducing rates of AIDS-related illness and death. Their effects can be monitored by measuring the amount of HIV in the blood, known as the viral load. An effective regimen should rapidly suppress the viral load to a level so low that it cannot be detected by the most sensitive tests available. However, this profound viral suppression certainly does not mean that the virus has been eradicated and the patient is cured; HIV persists at very low levels in the blood and tissues such as the lymph nodes, and if therapy is stopped, the viral load rapidly rebounds. Although successful viral suppression does appear to reduce the infectiousness of infected individuals, it does not eliminate it and cases of HIV transmission from individuals with suppressed viral load do occur.



The high cost of multi-drug combination therapy regimens has placed strain on the health services—even in developed countries such as the United Kingdom—and has to date rendered them almost entirely inaccessible for the developing world where most cases of HIV infection occur. At a time when they need more resources to combat HIV, African governments are paying four times more in external debt payments than they currently spend on health and education. In recent years, pressurized by the mounting toll of HIV in the developing world, legal actions, and activist campaigns, a number of pharmaceutical companies have made anti-HIV drugs available to developing countries at or below the price they cost to produce, but nevertheless, fewer than 4 per cent of people in need of antiretroviral treatment in low- and middle-income countries were receiving the drugs at the end of 2001.

باي. التكملة في الرد الجاي.

مرحبا. هذي التكملة.

[HIROSHI_11]

A Reverse Transcriptase Inhibitors



The development of antiviral drugs to attack HIV has targeted specific stages in the viral replication cycle. One such target is the requirement for HIV to undergo reverse transcription (the conversion of viral genomic RNA into DNA) at an early stage of infecting a host cell; this is a process unique to retroviruses and performed by the viral enzyme, reverse transcriptase (RT).



Nine of the approved anti-HIV agents are RT inhibitors. There are three different classes of RT inhibitors. The nucleoside analogue RT inhibitors (NRTIs) work as “DNA chain terminators”. That is, because each appears to be a normal nucleotide base (the building blocks of DNA), the RT enzyme mistakenly inserts the drug into the growing viral DNA chain. However, unlike normal nucleotide bases, the drugs cannot be further elongated (no additional DNA bases can be added once the drug is inserted) and therefore viral DNA synthesis is terminated. Nucleotide reverse transcriptase inhibitors (NtRTIs) are closely related to NRTIs. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) have a different mode of action; they are thought to inhibit RT by binding to the enzyme.



In the United States and Europe alike, six NRTIs have been approved for use: zidovudine (also known as ZDV or AZT and made by GlaxoSmithKline with the brand name Retrovir), didanosine (ddI or Videx, from Bristol-Myers Squibb), zalcitabine (ddC or Hivid, from Roche), stavudine (d4T or Zerit, from Bristol-Myers Squibb), lamivudine (3TC or Epivir, from GlaxoSmithKline), and abacavir (Ziagen, from GlaxoSmithKline). Two formulations that combine more than one NRTI in a single pill are also available: coformulated zidovudine plus lamivudine (Combivir), and coformulated zidovudine, lamivudine, and abacavir (Trizivir), both manufactured by GlaxoSmithKline. In addition, the NtRTI tenofovir (Viread, from Gilead) has been approved.



In the United States, three NNRTIs have been approved: nevirapine (Viramune, from Boehringer-Ingelheim), delavirdine (Rescriptor, from Pfizer), and efavirenz (Sustiva or Stocrin, marketed by Bristol-Myers Squibb in some countries and by Merck in others); nevirapine and efavirenz have also been approved in Europe. A number of additional NRTIs and NNRTIs are under development.



B Protease Inhibitors



The second major class of anti-HIV drugs is the protease inhibitors. These are drugs that specifically interfere with the action of the HIV protease enzyme.



Protease is employed at a later stage of the viral replication cycle, when new virus particles are being produced within an HIV-infected cell. The protein from which the core and envelope of the new particles will be formed is initially synthesized in a long strip, which has to be cut up by protease into smaller functional proteins. When the protease enzyme is inhibited, an HIV-infected cell can only produce immature, non-infectious viral progeny. In the United States and Europe, six protease inhibitors are licensed: saquinavir (available in two formulations, Fortovase or Invirase, from Roche), indinavir (Crixivan, from Merck Sharp & Dohme), ritonavir (Norvir, from Abbott), nelfinavir (Viracept, from Pfizer), amprenavir (Agenerase, from GlaxoSmithKline), and a combination pill containing lopinavir and ritonavir (Kaletra, from Abbott). Additional protease inhibitors are under development.



C Drug Resistance



One problem with all anti-HIV drugs produced to date is the development of viral resistance. HIV's replication process is relatively imprecise, resulting in the steady production of mutant variants of the virus, some of which are resistant to the effects of specific anti-HIV agents, meaning that they are able to replicate and cause immune damage despite the presence of the drug. The selective pressure exerted by treatment drugs means that within treated people these drug-resistant strains have a survival advantage over “wild-type” drug-sensitive strains, and over time they will replace the drug-sensitive strains as the dominant type of circulating virus. In such a patient the viral load starts to rise, reflecting increased rates of viral replication, and the disease course may revert towards that seen in untreated patients, with a falling CD4+ cell count and an increased risk of opportunistic conditions.



The appropriate therapeutic response is to change the treatment regimen to a different antiviral drug combination. However, the similarities between drugs in the same class mean that HIV that has become resistant to one NRTI may be cross-resistant to other NRTIs that the patient has not yet taken, and likewise within the NNRTI and protease inhibitor classes, thus limiting the patient's subsequent options for effective treatment. An important priority for companies developing new RT inhibitors or protease inhibitors is, therefore, to try to create agents that retain efficacy against HIV strains that have developed resistance to the agents that are already in use.



The development of resistance can be delayed or prevented by the use of potent HAART regimens. These combinations rapidly suppress viral replication to very low levels, thus preventing the evolution of mutant variants. To maximize the chances of a successful and durable response to antiretroviral therapy patients have to maintain very high rates of adherence to their drugs' dosing schedule, since missed doses allow the virus to replicate and thus provide it with the opportunity to develop resistance to the treatment regimen.



D Experimental Classes of Anti-HIV Drugs



The best hope of avoiding the problem of cross-resistance is to create entirely new classes of anti-HIV drugs. One such class currently in development consists of agents that may bind either to gp120 or to the cellular receptors to which gp120 attaches itself, thus interfering with the processes of viral binding, fusion, and infection of susceptible human cells. Enfuvirtide (also known as T-20 or Fuzeon, from Trimeris and Roche) is the first fusion inhibitor that has been shown to be effective among patients with extensive prior use of current antiretrovirals, and was approved for use during 2003.



Intensive research is under way into agents designed to inhibit HIV's integrase enzyme. Integrase enables HIV to incorporate its genetic material into the DFNA of a host cell, a vital step in the viral life cycle.



AIDS activists have campaigned vigorously for early access to experimental therapies for HIV. Community-based organizations such as NAM in the United Kingdom, or AIDS Treatment News and Project Inform in the United States, provide accessible information about new treatments and trials, helping individuals reach informed decisions about their options. Many infected people are willing to participate in clinical trials in the hope that experimental drugs may prove effective. Drug companies often provide pre-approval access to promising therapies through expanded access schemes and, in the United Kingdom, “named patient basis” prescribing.



E Gene Therapy



Gene therapy is also being studied as a potential treatment for HIV-infected people. One approach uses small molecules called anti-sense oligonucleotides, which bind to the viral RNA strand, preventing it from acting as a template for viral proteins. Another antiviral strategy uses molecules called ribozymes that can detect specific parts of HIV's RNA within infected cells and splice it, rendering it inactive.



Other researchers are using gene therapy to insert a gene into immune cells taken from infected people, either to boost the cellular immune response against HIV or to protect the CD4+ cells from infection. This is called adoptive cell therapy. The main problems with all these gene therapy approaches are delivering the new genes into cells, and ensuring that the altered cells are not identified as "foreign" and attacked by the host immune system.



F Immune-Based Therapies



It has become increasingly clear that the immune system is able to contribute significantly to the control of HIV in certain individuals. So-called long-term non-progressors, who are able to live with HIV for many years without signs of significant immune damage, tend to have strong and persistent immune responses that specifically target HIV. In most patients, however, initially strong HIV-specific immune responses rapidly wane. Several new approaches to therapy are designed to try to elicit and preserve HIV-specific immune responses in patients who lack them. There is preliminary evidence that starting antiviral therapy very promptly after initial infection may help to preserve HIV-specific immunity, and in some cases such individuals may be able to stop antiviral therapy and maintain very low levels of HIV replication. Other experimental strategies to try to generate HIV-specific immune responses include immunizations with therapeutic vaccines containing HIV antigens.



The drug interleukin-2 is being evaluated in large controlled studies. It stimulates the production of CD4+ T-cells, resulting in substantial increases in the patient's CD4+ cell count. The on-going studies are designed to see whether these artificially generated CD4+ cells provide effective immunologic protection against HIV-related conditions.



G Preventing and Treating Opportunistic Conditions



Use of potent antiretroviral regimens is now viewed as the best way to prevent HIV-infected patients from developing opportunistic conditions. Prior to the widespread use of HAART, however, many of the improvements in the quality and quantity of life among people with HIV resulted from better prophylactic (preventative) antimicrobial drugs to prevent or treat HIV-related opportunistic infections. Use of prophylaxis meant that many HIV-infected people did not now develop an AIDS-defining illness until they had reached an advanced stage of immune suppression. At present, most cases of HIV-related diseases occur in patients who have not received antiretroviral therapy, either by choice or because they were unaware that they were HIV-infected, or in those for whom antiretroviral therapy is no longer effective due to the development of viral resistance. In these patients, HIV-related diseases are treated with specific drugs, such as antibiotics for PCP, anti-fungal drugs for infections such as Cryptococcus, or antiviral drugs for CMV infections.



H Emerging Complications: Drug Toxicity and Viral Hepatitis



The advent of effective anti-HIV therapy has led to dramatic changes in the pattern of illnesses experienced by people with HIV. As the use of HAART regimens has become commonplace in the developed world, it has prevented or reversed damage to the immune systems of many HIV-infected people, so they are not at risk from the classic opportunistic conditions observed among immunosuppressed individuals. Many people who previously had to take prophylactic antimicrobial drugs to prevent the occurrence of HIV-related diseases have been able to discontinue those treatments and rely solely on anti-HIV drugs to maintain their immunologic function.



As opportunistic conditions have declined as causes of morbidity and mortality, treatment-related toxicities have increased in importance. HAART combinations can cause a relatively high rate of side-effects, including liver or kidney problems, nerve damage, nausea and vomiting, rashes, metabolic abnormalities including elevated levels of cholesterol and triglycerides, and disfiguring changes in the distribution of body fat. Most side-effects are not life threatening, however, and for individuals at significant risk of HIV-related disease the benefits of treatment far outweigh the costs in terms of toxicities. However, the risk/benefit equation is less clear-cut for individuals who have acquired HIV relatively recently and are unlikely to be at substantial risk of HIV-related complications for many years. For this reason, guidelines on the use of anti-HIV drugs recommend that they should generally be deferred until the patient's CD4+ cell count has declined to between 200 and 350 and they are at significant risk of developing AIDS-related conditions in the near future.



Co-infection with viral hepatitis, especially hepatitis C virus (HCV), is a growing problem among HIV-infected patients. Compared with HIV-negative persons who are infected with HCV, patients who have both HIV and HCV typically experience more rapid and more severe liver damage. Treating HIV does not of itself ameliorate hepatitis co-infection, and some anti-HIV drugs cause increased rates of liver toxicities in co-infected patients. A sizeable proportion of deaths among HIV-infected patients is now attributable to end-stage liver disease caused by viral hepatitis, even among patients whose HIV infection is well-controlled by anti-HIV therapy.

[HIROSHI_11]

VI PREVENTION AND EDUCATION



A Vaccines



Efforts are under way to develop an effective vaccine for HIV that could be either protective (preventing infection if an immunized person is exposed) or therapeutic (slowing immune destruction or prolonging survival in people who are already infected).



Most of the current experimental vaccines consist of one or more of HIV's structural proteins, such as the core protein p24 or the outer “envelope” proteins gp120 and gp160, used in combination with an adjuvant to boost the immune response.



Trials to date have been largely discouraging. Studies of several different therapeutic vaccines have found that some are immunogenic (they stimulate immune responses) but all have failed to show any effects on disease progression or survival rates. Ongoing studies are exploring whether the use of therapeutic vaccines combined with HAART may be more effective than current treatment strategies that use HAART alone.



Researchers working on preventive vaccines face a range of technical problems, including the difficulty of producing a vaccine that might offer protection against the range of HIV sub-types (or clades) found around the world, and HIV's ability to mutate rapidly so that its surface proteins are no longer recognized by the body's immune response. An effective vaccine would need to protect the individual against infection when exposed to either free HIV particles or HIV-infected cells, and to stimulate effective immune responses when the virus enters the body through the blood (such as during injecting drug use or occupational exposure) or across mucous membranes (such as during sexual intercourse).



The first large-scale efficacy trial of a protective HIV vaccine, AIDSVAX from VaxGen, ended in disappointment in 2003 when it was shown not to have slowed the progress of the disease. Scientists had earlier disagreed strongly over whether AIDSVAX, which was comprised of genetically engineered versions of the gp120 protein found on the surface of HIV, was likely to be effective. Several other large-scale preliminary studies of protective vaccine candidates are under way in high-risk populations such as gay and bisexual men, and in areas of the world with high incidence of HIV infection, such as Thailand, Brazil, and India. Some studies are evaluating a strategy known as "prime-boost", in which an initial immunization with one type of HIV vaccine is followed by a different type of vaccine, to try to stimulate different parts of the immune system. Although there have been promising results from animal tests of this approach, it will be many years before results of human studies are available.



B Prevention



HIV infection and AIDS are considered by many to be completely preventable, because the routes of HIV transmission are so well documented. It is clear that a reliable protective vaccine will not be available for many years. In the absence of a vaccine, the only means of preventing the spread of infection is to avoid personal behaviours that carry a risk of transmission. This has been the focus of AIDS education campaigns throughout the world.



B1 Safer Sex



Gay Pride Parade, 1993 Members of the activist group ACT UP (AIDS Coalition to Unleash Power) rally at a gay pride parade in New York in 1993. Such groups have helped raise public awareness about acquired immune deficiency syndrome (AIDS), which affects millions of people worldwide.Black Star/Richard Falco



Globally, the most common route of HIV transmission is through unprotected anal or vaginal intercourse. The risk can be eliminated by avoiding intercourse, or minimized by using a condom or "female condom", since HIV cannot pass through an intact latex barrier.



HIV transmission through oral sex is possible but rare, and AIDS organizations in most countries do not routinely recommend condom use for this activity.



Many safer sex campaigns have been conducted to encourage the general public and the groups most at risk from HIV to avoid unprotected sex. However, research on health promotion repeatedly shows that the simple provision of information is usually not in itself sufficient to lead to behaviour changes. That may require additional factors; for example, campaigns are more likely to succeed if they present acceptable and achievable options, and are reinforced by peer pressure in favour of certain forms of behaviour and against others.



The most successful safer sex campaigns were those conducted by and for urban gay communities in the 1980s, where the reduction in unprotected anal intercourse has been identified as the greatest health-related behaviour change ever achieved.



B2 Preventing Drugs-Related Infection



HIV transmission through drug-injecting equipment can be prevented by avoiding injecting drug use or by only using sterile equipment. Needle-exchange programmes have been introduced in many countries to minimize HIV transmission among drug users. In the United States such schemes are controversial as some regard them as condoning illegal drug use, but studies consistently show that needle exchanges are effective, leading to a lower incidence of HIV infection among injecting drug users.



B3 Heat Treatment of Donated Blood



In the early years of the epidemic, many cases of HIV transmission occurred through contaminated blood products and transfusions; the introduction of screening and heat treatment procedures means that infection through these routes is now extremely unlikely.



B4 AIDS Awareness Campaigns



AIDS Quilt The AIDS quilt travels on display to promote public awareness of acquired immune deficiency syndrome (AIDS). The quilt project, initiated in 1986 by the NAMES Project organization, consists of thousands of panels. Each panel is individually designed and is dedicated to the memory of someone who has died of AIDS.Woodfin Camp and Associates, Inc./A. Reininger



Prevention efforts to promote sexual awareness through sex education in schools have faced opposition from certain groups in society on the unfounded grounds that these efforts promote sexual promiscuity among young adults. Approaches such as requiring HIV-infected individuals (or their doctors) to disclose their HIV status to sexual partners, or mandating HIV testing at the time of marriage or pregnancy, have been criticized on the grounds that they may discourage HIV-infected individuals from coming forward for HIV testing. In these cases, issues of individual rights and personal privacy have to be weighed against their possible role in controlling the spread of HIV.



In recent years there has been intense debate about the proper allocation of AIDS education funds. In many countries, HIV transmission still occurs primarily among definable population groups and their sexual partners, yet the majority of resources have been spent on campaigns targeted at the general population rather than at the groups most at risk. In the United Kingdom, the Department of Health has recognized these criticisms and since the mid-1990s has stressed the importance of directing campaigns at gay and bisexual men and injection-drug users.



Prevention efforts through public awareness have been propelled by community-based organizations, such as the Terrence Higgins Trust in Britain, that provide current information to HIV-infected and at-risk individuals. Public figures and celebrities who are themselves HIV-infected or have died from AIDS, including Earvin "Magic" Johnson, Rock Hudson, and Freddie Mercury, have given a recognizable face to AIDS for society to come to terms with the enormity of the pandemic. In memory of those individuals who died from AIDS, especially in its early years, a giant quilt was made in 1986 by the US-based NAMES Project, where each panel of the quilt was in memory of an individual AIDS death.



further reading

These sources provide additional information on Acquired Immune Deficiency Syndrome.



In the United States, the government has also attempted to assist HIV-infected individuals through legislation and additional community funding measures. In 1990, HIV-infected individuals were included in the Americans with Disabilities Act so that it became illegal to discriminate against such individuals for jobs, housing, and other social benefits. A community funding programme to major US cities designed to assist the daily lives of individuals living with AIDS was established. There are currently no equivalent provisions made by central government in the United Kingdom and local health authorities and local councils may offer help to AIDS patients according to their own separate funding and policy provisions.

أختي المنتدى لا يسمح بوضع أكثر من 20000 حرف لذا اضطريت إلى كتابته في عدة ردود.



والسلام عليكم.

تحيات : أختك

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Hiroshi
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