Acquired immune deficiency syndrome (AIDS) is an advanced stage of infection with the human immunodeficiency virus (HIV). AIDS was first identified in 1981 in the United States and was subsequently identified around the world. HIV disease begins by causing the failure of the immune system, the development of any of a set of opportunistic infections (OIs), AIDS, and eventually death. Treatment of HIV disease has improved with the development of new drugs, increasing success at delaying symptoms and reducing mortality rates. However, treatment is not always effective, has significant side effects, is expensive, and is not universally available, especially among the poor and in developing countries.
HIV is a virus that is found most predominantly in body fluids containing white blood cells (e.g., blood, semen, breast milk, and cervical/vaginal secretions). HIV is most often transmitted when one of these body fluids from an infected person enters the blood system of an uninfected person through an opening in the body. HIV transmission most often occurs through sexual intercourse, sharing infected injection equipment involved in illicit drug use, breast-feeding, or transfusion of untested blood products, which does not occur in the developed world. Prevention of HIV infection generally involves modification of behaviors related to these modes of transmission.
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How Does The Immune System Function?
To understand HIV and AIDS, it is first necessary to understand some rudimentary principles of how the immune system functions. Intact skin is the first component of a functioning immune system. Skin provides a barrier against many infections, including HIV. If an infectious agent such as HIV gets past that first barrier, either through an existing opening, such as a mucosal membrane (e.g., vaginal, anal, urethral tissue) or through a puncture (e.g., injection drug use), the cell-mediated immune system responds to the infection. Generally, the immune system consists of a collection of different types of cells, each of which plays a different role in a sequence of steps that collectively create an immune response. All parts of the immune system are necessary to ensure an unimpaired immune response.
First, a foreign particle such as HIV is introduced into the body. The foreign body is an antigen. The antigen is identified as foreign by immune cells known as macrophages. These cells interact with T4 cells (also known as T helper, or TH, cells and as CD4+ cells), activating the T4 cell. Once activated, the T4 cells secrete lymphokines (e.g., gamma interferon) and begin to divide and replicate. This activity subsequently causes B lymphocytes, or B cells, to multiply and produce antibodies. Antibodies bind to the specific antigen, marking it for destruction. Cytotoxic T lymphocytes (also known as T8 cells) eliminate virus infected cells. After this infection is resolved, T and B memory cells remain to provide a quick immune response in the case of reinfection with the same antigen. In addition, remaining antibodies provide humoral immunity against future reinfection.
How Does HIV Interfere With Immune System Functioning?
HIV binds specifically to cells that have the CD4 receptor on their exterior membrane. Therefore, the T4 cell, which is also designated as CD4+ to indicate the presence of this receptor, is one of the cells that HIV can infect. Once HIV binds to the T4 cell, which also involves binding to the fusin and CC-CKR-5 receptors on the cell membrane, it passes through the cell membrane into the T4 cell. Inside the T4 cell, the virus sheds the protein coat, releasing the viral genetic material, which is RNA, into the cell. Next, the viral RNA is converted into viral DNA by an enzyme reverse transcriptase. The viral DNA moves into the nucleus of the T4 cell, where it becomes part of the human DNA with the involvement of the enzyme integrase. Subsequently, the merged genetic material begins to manufacture new viral RNA at a high rate. The viral RNA moves out of the nucleus, to the outer cell membrane. Proteins are processed into shorter lengths with the enzyme protease. Immature HIV buds out of the membrane, creating a new HIV virus. This process leaves a pockmark where the HIV viral bud bursts from the T4 cell membrane. The replication of thousands of new HIV cells from the T4 cell eventually kills the T4 cell and releases those thousands of HIV cells to repeat the process with other T4 cells. Through this process, the viral load (number of HIV cells in the blood) increases and the number of T4 cells decreases over time. Because T4 cells play an important role in the sequence of cell-mediated immune functioning, the reduction in T4 cells parallels the decrease in immune function.
How Does HIV Cause HIV Disease And AIDS?
Laboratory tests can monitor T4 cell counts. Normal blood levels are 800 to 1200 per microliter (µL) of blood. Over time, HIV replication causes decreases in T4 cell counts. As the level decreases, immune system function also decreases. The impaired immune system fails to respond effectively to other infections, leaving the person more prone to becoming ill from common infections. These infections are OIs because they appear to take advantage of the opportunity of an impaired immune system. Typically, these OIs are significant or life-threatening only in people with impaired immune systems (e.g., newborn babies, elderly people, patients whose immune systems have been impaired by radiation or chemotherapy).
When T4 counts drop below 500, some OIs begin to appear. Below 200, the risk for OI becomes significant. For this reason, a T4 count below 200 in an HIV-positive person is enough to diagnose that person as having AIDS. Alternatively, an HIV-positive person is diagnosed with AIDS when he or she has a T4 cell count higher than 200 and 1 of the 26 defining OIs. The average length of time from infection to development of symptoms of AIDS is about 11 years. This period may be extended with antiviral medications.
The 26 defining OIs are candidiasis of bronchi, trachea, or lungs; candidiasis, esophageal; cervical cancer, invasive; coccidioidomycosis, disseminated or extrapulmonary; cryptococcosis, extrapulmonary; cryptosporidiosis, chronic intestinal; cytomegalovirus disease; cytomegalovirus retinitis with loss of vision; HIV encephalopathy; herpes simplex (chronic ulcers or bronchitis, pneumonitis, or esophagitis); histoplasmosis, disseminated or extrapulmonary; isosporiasis, chronic intestinal; Kaposi’s sarcoma; lymphoma, Burkitt’s; lymphoma, immunoblastic; lymphoma, primary in brain; Mycobacterium avium complex, disseminated or extrapulmonary; Mycobacterium kansasii, disseminated or extrapulmonary; Mycobacterium tuberculosis, disseminated or extrapulmonary; Mycobacterium, other species or unidentified species, disseminated or extrapulmonary; Pneumocystis carinii pneumonia; pneumonia, recurrent; progressive multifocal leukoencephalopathy; salmonella septicemia, recurrent; toxoplasmosis of brain; and wasting syndrome due to HIV.
As a person who is infected with HIV continues to lose T4 cells to HIV replication, multiple OIs are likely to develop. Most people with AIDS die of an OI.
How Are HIV And Aids Treated?
Medical intervention for HIV infection, disease, and AIDS begins with the identification of HIV infection. This is done using a lab test to identify antibodies to HIV present in the blood. Because all viruses, including HIV, are very small, it is easier to identify antibodies to the virus than the virus itself. Therefore, the HIV antibody test is used to identify HIV infection. However, this means that the blood test will only identify infection after antibodies have developed, which can take weeks to months. Many HIV-infected people develop antibodies to the virus within 6 weeks, with almost all developing antibodies within 3 months. Nearly 100% of HIV-positive people develop antibodies within 6 months. The period between actual infection and the development of detectable antibodies is known as the window period. Because of this window period, a person who is concerned about possible infection must wait to take an antibody test. If the test is negative, the person is generally encouraged to return in several months for another test to be sure that the result is actually negative. Alternatively, a more sensitive test for the actual virus can be performed, a viral load test. This test is more expensive and therefore is usually reserved to monitor known infection and treatment effectiveness.
Originally, HIV antibody tests were performed on blood samples drawn from the arm, with tests performed at a lab taking several weeks to return results. Therefore, people needed to return for their results. These procedures had several barriers to serving the population. Some people are uncomfortable with blood draws. Many who had initially elected to be tested did not return to receive their results. Newer technology has allowed for home collection of a spot of blood for mail-in testing, needle-free tests performed on cells swabbed from inside the mouth, and most recently, doctor’s office testing allowing test results to be given within minutes. Nevertheless, these procedures require initiative on the part of the person to find out his or her HIV status. Currently, most people who are infected with HIV, both in the United States and globally, do not know it.
Once a person is diagnosed as being infected with HIV, or as being HIV positive, medical monitoring and treatment may proceed if available and affordable. Monitoring of health status generally includes T4 cell counts in the blood. In addition, viral load may be monitored using viral load tests. High levels of viral load generally parallel decreases in T4 cell counts, marking immune impairment and predicting risk for developing OIs.
As HIV disease progresses, drug treatment may be implemented, if available and affordable. Drug treatment centers on antiviral medications. Antiviral drugs work by interrupting the processes required for the virus to enter the T4 cell and to use the cell to replicate. There are several different types of antiviral medications used to treat HIV disease. The first type of antiviral developed was a reverse transcriptase inhibitor. These drugs interfere with HIV replication in the T4 cell by inhibiting the enzyme reverse transcriptase and the process of turning viral RNA into DNA. The second type of antiviral drug developed was a protease inhibitor. These drugs interfere with HIV replication by inhibiting the enzyme protease and the process of cutting proteins to the appropriate length for creation of new HIV. Drugs designed to inhibit the integrase enzyme and to block the attachment of HIV to the fusin protein are in development. However, current HIV treatment uses a combination of drugs to inhibit viral replication. This approach, combination therapy, cocktail therapy, or more specifically, highly active antiretroviral treatment (HAART), uses drugs of different types. For example, a common combination includes two reverse transcriptase inhibitors and one protease inhibitor. This treatment has been found to reduce viral load below detectable levels in many patients. The virus is not eliminated, and interruptions of HAART lead to rebounds in viral load, but with low viral loads, T4 cell counts have been found to increase. With increased T4 cell counts, OIs are naturally reduced. HIV-positive patients on HAART often return to healthy status. AIDS mortality rates in the United States dropped by 50% following the approval of HAART.
Unfortunately, these powerful medications are costly, are not universally or permanently effective, and have significant side effects. In many developing countries, treatment for HIV is unavailable. Some HIV-positive patients find that HAART is not effective because their HIV virus is a drug-resistant strain. Others may find that over time these mutations develop and their own HIV becomes drug resistant, leading to increased viral load, decreased T4 cell counts, development of OIs, and progression of AIDS. Finally, the medications themselves have some very toxic side effects. For example, recent research has reported a twofold to threefold increase in the risk for heart attack among people with HIV taking protease inhibitor medications for 2 to 3 years.
How Is HIV Transmitted?
HIV is transmitted when HIV-positive body fluids that are rich in white blood cells enter the body of an HIV-negative person. Because transmission requires the presence of an HIV-positive person, a spilling of body fluid, and direct entry into an opening of an HIVnegative person, HIV is not transmitted easily or in casual contact. Without direct transmission of body fluids into another person, HIV transmission does not occur. Also, HIV does not live long outside of a human body. HIV transmission is generally associated with four body fluids: blood, semen, cervical-vaginal secretions, and breast milk. For these reasons, caregivers, family members, co-workers, and classmates generally do not need to be concerned about HIV transmission.
Work-site transmission of HIV has only been documented with skin punctures (e.g., needle sticks) or heavy exposure of blood spilled onto mucosal membranes or open wounds (e.g., weeping eczema). Universal precautions, which involve use of protection from exposure to blood and body fluids from all patients, are the standard in health care and prevent HIV transmission.
Transmission of HIV by blood has been mainly associated with untested blood transfusions and sharing of injection equipment by illicit drug users. Donated blood has been universally tested in the United States since 1985. Therefore, HIV transmission by transfusion is largely unknown. HIV is not transmitted to blood donors. Injection drug users (e.g., intravenous heroin users) often share needles and other injection equipment because such equipment is scarce. The reason injection equipment is scarce is that, in efforts to control such drug use, injection equipment has been made available only by prescription (e.g., to diabetics) and is illegal to carry without such a prescription. This means that drug users may share a common set of works or rent the equipment from the drug dealer. In some states, efforts to decrease this mode of HIV transmission have led to more drug treatment, clean needle exchange programs, distribution of bleach and water kits to disinfect injection equipment, and the availability of syringes without prescription in some states.
Transmission of HIV through semen and cervical-vaginal secretions has been the major mode of transmission. Sexual transmission of HIV accounts for most cases of HIV. Historically, the first cases of AIDS identified in the United States were among homosexual men. Globally, however, most cases of AIDS were transmitted through heterosexual contact. In most countries, AIDS cases are equally prevalent among men and women. Prevention of sexual transmission involves abstinence, condom use, and HIV testing and knowledge of status paired with discussion of HIV and prevention with sexual partners.
HIV transmission from mother to child (i.e., vertical transmission) may occur prenatally, at birth, or through breast milk. If a pregnant woman is HIV positive and is not taking antiviral medications, there is a 25% to 30% chance that the baby will be HIV positive. If the mother is treated with even one reverse transcriptase inhibitor, the chance of transmission drops to 8%. Therefore, HIV testing of pregnant women is important in order to initiate antiviral treatment for mother and to protect the fetus. Also, because most babies born to HIV-positive mothers are not HIV positive, transmission through breast milk is an important issue. If a woman is HIV positive and her child is HIV negative, she should not breast-feed. However, in developing countries, formula may be unavailable or too expensive, or the water to mix the formula may not be safe. If a child is born HIV negative to an HIV-positive mother, the probability of this child eventually being orphaned is also significant.
HIV testing of newborns requires the use of more expensive viral load tests because the child’s blood will contain antibodies from the mother, including HIV antibodies, even if the child does not carry the virus itself. Therefore, newborns of HIV-positive mothers must either be tested with viral load tests or treated with antivirals during the 18 months that it can take to clear maternal antibodies and develop detectable HIV antibodies reflective of the child’s own HIV status. Also, during that period, breast-feeding would increase the risk for virus transmission to a previously HIV-negative newborn.
How Can HIV Transmission Be Prevented?
Work on treatment issues parallels work to prevent HIV infection. Vaccines to prevent HIV disease are in clinical trials, but early results have been unsatisfactory. Risk behavior reduction has been the most effective intervention to date. Significant reductions in transmission have been effected with communitywide campaigns to reduce the riskiest behaviors or to modify them to make them safer (e.g., with condoms or with clean injection equipment). Nevertheless, much remains to be done to reduce the rate of growth, much less eradicate the scourge, of HIV and AIDS worldwide.
Prevention of transmission of HIV through blood has focused on testing the transfusion blood supply. With universal testing of blood products, transfusion related transmission of HIV has been virtually eliminated. Also, modification of illicit drug use behaviors is an important mechanism for preventing blood-to-blood transmission of HIV. Drug treatment to promote abstinence or replacement of injection drugs with prescription oral medications such as methadone is one way to reduce HIV transmission among drug users. Alternatively, approaches known as harm reduction, which focus on reducing risks, even if drug use itself is not reduced, have been effective in decreasing HIV transmission. One harm-reduction approach is to distribute bleach and water kits to drug users to allow them to clean equipment between users. The technique is to flush the syringe with bleach twice and then with clean water twice. It is important that drug users also not share other pieces of equipment such as cookers.
Another harm-reduction approach is syringe exchange programs. These are programs in which injection drug users return used, contaminated syringes and are given the same number of clean syringes. Research has countered concerns about this technique. Critics suggested that drug users would use more drugs or would delay seeking treatment. Critics also suggested that the number of drug users would increase. Research has repeatedly countered these concerns by documenting decreased drug use, earlier treatment seeking, and no increase in the number of drug users. Decreases in HIV transmission have been documented. In addition, some states have made syringes available without prescription in order to decrease the need to share needles and subsequently transmit HIV.
Sexual transmission of HIV is the most common form of transmission. Methods of reducing sexual HIV transmission include abstinence, safer sex (condoms, lower risk behavior, fewer partners), and HIV testing and discussion. Abstinence is the only certain method of preventing HIV transmission; however, it is not an acceptable method for many people. For people who do engage in sex and want to reduce their risk for HIV, health education workers have advocated safer sex. Safer sex methods include modifying sexual behavior to avoid high-risk penetrative sex (vaginal or anal) for a lower-risk penetrative (oral) or nonpenetrative (mutual masturbation, frottage) sexual behavior. Penetrative sex can be made safer by using male or female condoms. Also, the odds of encountering an HIV-positive person may be reduced simply by having fewer partners. Another method of reducing sexual HIV transmission is to engage in HIV testing before engaging in sex with a new partner and to discuss HIV status and prevention before having sex. This requires preplanning, interpersonal skills, and the ability to wait for repeat testing after the period of undetectable infection (3 to 6 months) has passed.
In the event of an unintentional exposure to HIV, either through a needle stick in a health care facility, through a sexual assault, or through a voluntary sexual episode, post-exposure prophylaxis has been used to reduce the risk of the exposure becoming an active infection. This technique is to administer antiviral medications for 1 month, beginning within 72 hours after the accidental exposure. In theory, any virus that may have entered the body may be prevented from replicating and therefore never establish itself as an infection able to sustain itself. After a month, viral load testing can evaluate the presence or absence of HIV.
What Is The History Of AIDS In The United States And Globally?
In 1981, AIDS was first identified when a number of patients died soon after presenting with a puzzling set of conditions. Previously healthy young men presented to physicians in San Francisco and New York City with Pneumocystis carinii pneumonia (PCP) and Kaposi’s sarcoma (KS). PCP is a form of pneumonia usually seen only among newborns, the elderly, and cancer patients whose immune systems have been suppressed by chemotherapy. KS is a cancer of the lining of the blood vessels, appearing as purplish lesions on the skin, which normally appears among elderly men of Mediterranean descent, is usually slow to progress, and is generally not fatal. In 1981, it was reported that 41 young homosexual men had presented with these disorders and that 8 had died within 2 years. The Centers for Disease Control and Prevention in Atlanta released this news in the Morbidity and Mortality Weekly Report on June 5, 1981. The New York Times was the first to publish this news in the lay press on July 3, 1981.
Until 1983, it was not clear what was causing this syndrome of immunodeficiency-related conditions. In 1983, Dr. Robert Gallo in the United States and Dr. Luc Montagnier in France independently reported that the cause of AIDS was a virus. Gallo called the virus human T-cell lymphotropic virus type III (HTLV-III). Montagnier called the virus lymphadenopathyassociated virus (LAV). There was a dispute about who had made the discovery first. Nevertheless, the World Health Organization (WHO) renamed the virus the human immunodeficiency virus (HIV).
Until 1985, there was no way for persons to know whether they had been infected with the virus. Because there is a lag of years between infection and development of symptoms, many people could be transmitting the virus without knowing that they were infected. In 1985, the U.S. Food and Drug Administration (FDA) approved the HIV antibody test. This development allowed people to determine their HIV status.
Many people did not take the HIV test under the rationale that there was no reason to know because there was no antiviral treatment. At that time, treatment focused on symptomatic OIs in attempts to delay mortality and improve remaining quality of life. In 1987, the FDA approved the first antiviral for treatment of HIV. This medication was a reverse transcriptase inhibitor, zidovudine (ZDV or AZT), marketed as Retrovir. There were equivocal results in tests of the effectiveness of treatment with this medication. There were questions as to whether it extended life. There was evidence that OIs were delayed, even if death was not delayed. This suggested that the medication could provide better quality of life, if not greater quantity of life.
Several other reverse transcriptase inhibitors were developed in the 1990s, but it was not until 1995 that a significantly new type of antiviral medication was approved by the FDA. In 1995, the protease inhibitor saquinavir mesylate, marketed as Invirase, was approved. Subsequently, other protease inhibitors have been developed and approved. Currently, HAART involves multiple medications, usually two reverse transcriptase inhibitors and one protease inhibitor. Combination therapies were approved in 2000, which showed significant effects at reducing viral load, morbidity (i.e., illness), and mortality. In fact, AIDS mortality in the United States dropped by about 50% with the development of HAART. With future developments of fusin blockers and integrase inhibitors, it may be expected that combination therapies may become even more effective.
What Is The Global Impact Of HIV?
In the United States, there have been 886,575 cases of AIDS diagnosed from 1981 through 2002. Of those, 501,669 patients had died by the end of 2002. Globally, there were about 40 million people living with HIV during 2003. Of those, about 5 million were newly infected during 2003. Worldwide, 3 million people died of AIDS in 2003. It is important to note that HIV and AIDS are not evenly distributed around the world. As of 2003, not only are a large number of HIV and AIDS cases found in sub-Saharan Africa (25.0 to 28.2 million infections) and South and Southeast Asia (4.6 to 8.2 million infections), but also the prevalence of HIV and AIDS is disproportionately centered on certain regions in the developing world. Specifically, the adult prevalence rate is highest in sub-Saharan Africa (7.5–8.5%) and the Caribbean (1.9–3.1%), as compared with North America (0.5–0.7%). Similarly, AIDS deaths have been highest in sub-Saharan Africa, with 2.2 to 2.4 million deaths during 2003. South and Southeast Asia experienced 330,000 to 590,000 deaths in 2003. These were the highest number of deaths, especially as compared with North America (12,000–18,000 deaths) and Australia and New Zealand (less than 100 deaths).
It is important to note that in areas such as subSaharan Africa, the high infection, illness, and death rates not only are affecting society as a whole but also are generally concentrated among adults of childbearing age because of the nature of HIV as a sexually transmitted infection. This means that as that cohort is ill and dying, the region is affected by a workforce that is ill and dying and by a generation of parents who are ill and dying, leaving a generation of children orphaned. Workforce productivity, agricultural productivity, and economic vitality are being severely affected by the HIV pandemic.
To respond to the HIV pandemic, these developing nations are significantly limited in their economic ability to provide medical treatment and associated services to people with HIV and AIDS. Therefore, in many of these regions, HIV is left largely untreated, with a morbidity and mortality profile similar to that of HIV in the United States during the 1980s. Specifically, with no antiviral treatment, infection progresses to AIDS unchecked, with a life span of about 2 years after AIDS diagnosis.
Summary And Conclusion
Not only does the economic status of countries or regions interact with HIV and AIDS, but also specific cultural factors within each region are affected. Specifically, factors that interact with HIV transmission and prevention efforts include levels of education in general, HIV education specifically, poverty and the subsequent influence of injection drug use and prostitution, and the rights of women and their freedom and economic viability to self-determination. All these cultural factors are relevant and must be included in the consideration of prevention and treatment efforts. Overall, it is important to consider the scientific and cultural factors relevant to the prevention and treatment of HIV and AIDS in order to implement effective responses to this pandemic.
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