The AIDS Pandemic

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The AIDS Pandemic

Overview

Acquired Immune Deficiency Syndrome (AIDS) was first identified in 1981. This complex disease is characterized by the breakdown of the body's immunologic defense system, which results in vulnerability to many normally harmless microorganisms. The causal agent, a human retrovirus now known as the human immunodeficiency virus (HIV), was discovered in 1984. Despite the growing toll of the global AIDS crisis and the absence of a preventive vaccine as well as the lack of safe and affordable therapeutic drugs, by 1995 epidemiologists in the United States were warning policy makers and the public about a growing complacency towards AIDS.

Background

AIDS first appeared as a diagnostic entity in 1981, when the Centers for Disease Control (CDC) began to report strange clusters of rare illnesses, such as Pneumocystis carinii pneumonia (PCP) and Kaposi's sarcoma, in previously healthy homosexual men in New York and California. These diseases were associated with a severely compromised condition of the immune system. Within five years of the first reports, the U.S. Public Health Service estimated that more than one million Americans were infected with HIV. By the end of 1994, the CDC had gathered reports of over 400,000 cases of AIDS, including 170,870 AIDS-related deaths. In the United States, AIDS quickly became one of the leading causes of death in adults aged 26 to 44. The disease also increased rapidly in Africa, South America, Western Europe, and Asia. Studies published by the World Health Organization (WHO) indicated that within ten years of the discovery of AIDS, five to ten million people were infected with HIV. In contrast to the pattern in the United States, in Africa AIDS was first recognized in sexually active heterosexuals, and AIDS cases in Africa have occurred at least as frequently in women as in men. Overall, the worldwide distribution of HIV/AIDS between men and women is approximately 1 to 1.

The human immunodeficiency virus (HIV), the retrovirus that causes AIDS, was discovered in 1984. Robert Gallo (1937- ), at the National Institutes of Health, and Luc Montagnier (1932- ), at the Pasteur Institute, are generally regarded as the discoverers of the virus. A test to identify AIDS antibodies, and thus screen for the disease, was developed at about the same time. Studies of previously stored blood samples suggest that the virus probably entered the U.S. population sometime in the late 1970s.

Retroviruses have genes composed of ribonucleic acid (RNA) molecules, rather than deoxyribonucleic acid (DNA). Although all viruses only can reproduce inside cells, retroviruses must use an enzyme called reverse transcriptase (RT) to convert their RNA into DNA. Because HIV RT makes many mistakes while making DNA copies from HIV RNA, many variants of the virus develop in an infected individual. A viral enzyme called HIV integrase splices the viral DNA into the host cell's DNA. When the viral DNA is incorporated into the cell's genes it is known as a "provirus." HIV belongs to a subgroup of retroviruses known as lentiviruses, or "slow" viruses. The interval between the initial infection and the onset of serious symptoms is generally quite long and variable. Eventually, immature viral particles form and acquire an envelope. In order to create infectious viral particles, an enzyme called protease has to cut long chains of proteins in the immature viral core into smaller pieces. HIV replicates so rapidly that several billion new virus particles can be produced every day. Some immune cells become infected but are not destroyed by the virus. Such cells can carry HIV to various organs, including the lungs and brain. Debilitating weight loss, diarrhea, neurologic conditions, and cancers, such as Kaposi's sarcoma and lymphomas, characterize the terminal stage of AIDS.

The time interval between infection with HIV and the development of AIDS-related symptoms is quite variable, sometimes as short as two years but usually about 10 to 12 years. Although the evidence that HIV is the etiological (causal) agent for AIDS appears to be very strong, some critics have proposed alternative explanations for the AIDS epidemic. One of the most vocal and prominent of these critics is Peter Duesberg, professor of molecular and cell biology at the University of California at Berkeley and author of Inventing the AIDS Virus. Nevertheless, increasingly sensitive testing methods, including the polymerase chain reaction (PCR), have strengthened the link between HIV infection and the development of AIDS. By the second decade of the AIDS crisis more than 1,000 journal articles and books on AIDS and HIV were being published every month. The National Library of Medicine dedicated AIDSLINE and other medical databases to writings on the disease and published a monthly AIDS Bibliography.

Impact

By 1999, the number of people worldwide living with HIV/AIDS was estimated at 33 million; almost 70% of these people lived in Sub-Saharan Africa. Through 1997, cumulative HIV/AIDS-associated deaths worldwide numbered approximately 12 million. By the end of 1998, the estimate for cumulative HIV/AIDS-associated deaths worldwide was about 13.9 million: 10.7 million adults and 3.2 million children. Africa has been particularly burdened by AIDS. In some African countries, the rate of HIV infection among adults aged 15 to 49 exceeds 20%.

When AIDS was first recognized in 1981, patients generally died within a year or two of the diagnosis. By 1995, studies of AIDS and HIV helped scientists develop more effective ways of combining anti-viral drugs and provided the basis for the development of new anti-HIV drugs that have prolonged the life span and enhanced the health of HIV-positive individuals. Basic research concerning the mechanism by which the virus attacks the immune system indicated that suppressing HIV replication could delay or prevent the progression of the disease.

The drugs originally used to treat HIV infection were nucleoside analogue reverse transcriptase (RT) inhibitors, which act by interfering with the action of HIV reverse transcriptase. The first of these drugs, zidovudine (AZT), was originally developed in 1964 as a possible cancer treatment. In the early 1980s AZT was found capable of suppressing HIV replication in the test tube; this discovery led to clinical trials of AZT and other nucleoside RT inhibitors, including zalcitabine (ddC), didanosine (ddI), stavudine (D4T), and lamivudine (3TC). HIV, however, mutates rapidly and quickly develops resistance to anti-HIV drugs. Researchers discovered that using combinations of drugs helped overcome this problem.

Although the drugs used to treat AIDS are known to have serious side effects and are very expensive, most authorities believe that their benefits outweigh the dangers. Critics, however, continue to raise doubts about the cause of AIDS as well as the safety of the drug regimens used to treat the disease. For example, South Africa's President Thabo Mbeki asserted in a speech before the South African parliament in October 1999 that AZT was unsafe. (South Africa has one of the highest incidences of AIDS cases; about 8% of the population, some 3.6 million people, are estimated to be HIV positive.)

AZT is one of the oldest and best known of the drugs used in the treatment of AIDS and has also been given to infected women to prevent the transmission of HIV to their babies during birth. By 1999, four protease inhibitors—saquinavir, ritonavir, indinavir, and nelfinavir—had been approved for marketing in the United States. Combinations of protease inhibitors and other categories of drugs can dramatically reduce the levels of HIV in the blood, although the virus appears to persist in certain cells. Other insights into the mechanisms of HIV replication suggest new targets for anti-HIV drugs as well as new ways to fight other diseases, such as hepatitis, influenza, and cancer.

Unfortunately, many patients cannot tolerate the available drug regimens. Moreover, most of the 30 million people worldwide who are infected with HIV cannot afford the drug regimens currently showing such promise in the United States. Given the expense and complexity of anti-HIV therapies, the development of a safe and effective vaccine for AIDS remains a public health priority throughout the world. At the end of the twentieth century, researchers continue to develop and test novel experimental HIV vaccines as well as vaccine adjuvants (compounds that enhance the immune response to vaccines).

Many social critics have argued that AIDS has exerted a profound influence on politics, science, art, the health care system, and the legal system as well as on biomedical research and resources. AIDS activists have succeeded in getting more research funding dedicated to AIDS research; they have changed the nature of clinical trials for AIDS drugs, asserted a right to privacy, called for nondiscrimination in the workplace and health care system, and renewed the debate about "pure research" vs. "mission-oriented research." Their successes have led those concerned with other diseases to adopt similar tactics. AIDS activists have demanded a more rapid review and approval process for new AIDS drugs, but the problem of evaluating quack remedies has become even more acute under current circumstances. While many critics argue that AIDS has had an adverse impact on American research priorities, the AIDS crisis is distinct because it is enmeshed in many complex social problems, including substance abuse, prostitution, homelessness, poverty, privacy issues, the legal rights of infected individuals, resource allocation, and the deteriorating infrastructure of our public health system.

Further studies of HIV have suggested that the virus had probably been incubating as a silent epidemic in areas of the world where the deaths of children and young adults from fevers and diarrheal diseases were not at all uncommon. AIDS has made it clear that the most powerful antibiotics are ultimately powerless against the onslaught of microbial agents if the body's own immunological defenses cannot participate in the battle. The AIDS pandemic may, therefore, stimulate renewed interest in public health medicine and the need for preventive immunizations. The fears generated by AIDS as well as the recognition of the general threat posed by newly emerging viruses may also reverse the tendency of wealthy nations to assume that infectious diseases have been conquered and that previously obscure third world diseases are inconsequential.

LOIS N. MAGNER