Acquired Immune Deficiency Syndrome (AIDS) – Characteristics, History and Postscript
Acquired immune deficiency syndrome (AIDS), first identified in 1981, is an infectious disease characterized by failure of the body’s immunologic system. Affected individuals become increasingly vulnerable to many normally harmless microorganisms, eventually leading to severe morbidity and high mortality. The infection, spread sexually and through blood, has a high fatality rate, approaching 100 percent. Caused by a human retrovirus known as HIV-1, AIDS can now be found throughout the world – in both industrialized countries and developing nations. Public-health officials throughout the world have focused attention on this pandemic and its potentially catastrophic impact on health, resources, and social structure. treatments for the disease have been developed, but no cure or vaccine currently exists.
Beginning in the late 1970s, physicians in New York and California reported increasing incidence of a rare cancer, Kaposi’s sarcoma, and a variety of infections including pneumocystis pneumonia among previously healthy young homosexual men. Because of the unusual character of these diseases, which are typically associated with failure of the immune system, epidemiologists began seeking clues that might link these cases. AIDS was first formally described in 1981, although it now appears that the virus causing the disease was silently spreading in a number of populations during the previous decade. Early epidemiological studies suggested that homosexual men, blood recipients (especially hemophiliacs), and intravenous drug users were at greatest risk. Re-search focused on searching for an infectious agent transmitted sexually or through blood. In 1983, in French and American laboratories, an unknown human retrovirus was identified and named HIV-1 for “human immunodeficiency virus.” Although the biological and geographic origins of the organism remain obscure, the AIDS epidemic appears to mark the first time it has spread widely in human populations. No evidence exists for casual transmission of HIV.
Following identification of HIV-1, tests to detect antibodies against it were devised in 1984. Although these tests do not detect the virus itself, they are generally effective in identify-ing infection because high levels of antibody are produced in most infected individuals. The enzyme-linked immunosorbent assay (ELISA), followed by Western blot testing, has enabled the screening of donated blood to protect the blood supply from HIV, as well as testing for epidemiological and diagnostic purposes.
As HIV infection precedes the development of AIDS, often by several years, the precise parameters of the epidemic have been difficult to define. Although “cofactors” that may deter-mine the onset of symptoms remain unknown, evidence suggests that HIV-infected individuals will eventually develop AIDS.
Researchers have identified three epidemiological patterns of HIV transmission, which roughly follow geographic boundaries. Pattern I includes North America, Western Europe, Australia, New Zealand, and many urban centers in Latin America. In these industrial, highly developed areas, transmission has been pre-dominantly among homosexual and bisexual men. Since the introduction of widespread blood screening, transmission via blood in these areas now occurs principally among intravenous drug users who share injection equipment. Although little evidence exists of widespread infection among heterosexuals in these countries, heterosexual transmission from those infected intravenously has increased, leading to a rise in pediatric cases resulting from perinatal transmission.
Within the United States, distribution of AIDS has been marked by disproportionate representation of minorities and the poor. As the principal mode of transmission has shifted to intravenous drug use, AIDS has increasingly be-come an affliction of the urban underclass. surveys reveal that 50 percent or more of intravenous drug users in New York City are infected with HIV. Women are typically infected by intravenous drug use or by sexual contact with a drug user.
In pattern II countries, comprised of sub-Saharan Africa and, increasingly, Latin America, transmission of HIV occurs predominantly through heterosexual contact. In some urban areas in these countries, up to 25 percent of all sexually active adults are reported to be infected, and a majority of female prostitutes are seropositive. Transfusion remains a mode of transmission because universal blood screening is not routine. Unsterile injections and medical procedures may also contribute to the spread of infection. In these areas, perinatal transmission is an important aspect of the epidemic.
Pattern III countries, including North Africa, the Middle East, Eastern Europe, Asia, and the Pacific, initially experienced less morbidity and mortality from the pandemic. Apparently, HIV-1 was not present in these areas until the mid-1980s. The nature of world travel, however, has diminished the significance of geographic isolation as a means of protecting a population from contact with a pathogen.
In 1985, a related virus, HIV-2, was discovered in West Africa. Although early reports suggested that HIV-2 is less pathogenic, the natural history of this agent remains unclear, as does its prevalence.
HIV cripples the body’s immunologic system, making an infected individual vulnerable to other disease-causing agents in the environment. The most common of these opportunistic infections in AIDS patients has been pneumocystis pneumonia, previously seen principally in patients receiving immunosuppressive drugs. In addition to pneumocystis, AIDS patients are prone to other infectious agents such as cytomegalovirus, Candida albicans (a yeast like fungus), and Toxoplasma gondii (a protozoan parasite). Moreover, a resurgence of tuberculosis has been reported in nations with high AIDS incidence.
Immunologic damage occurs by depletion of a specific type of white blood cell called a helper T4 lymphocyte. Destruction of these cells ac-counts for the vulnerability to normally harm-less infectious agents. In some cases, infection of the central nervous system with HIV may cause damage to the brain and spinal column, result-ing in severe cognitive and motor dysfunction. In its late manifestations, AIDS causes severe wasting. Death may occur from infection, functional failure of the central nervous system, or starvation.
HIV infection has a wide spectrum of clinical manifestations. After infection, an individual may remain free of symptoms for years, even a decade or longer. Some individuals experience fever, rash, and malaise at the time of infection when antibodies are first produced. Patients commonly present with general lymphadenopathy, weight loss, diarrhea, or an opportunistic infection. Diagnosis is confirmed by finding antibodies for HIV or by a decline in T4 cells. Most experts now agree that HIV infection itself be considered a disease, regardless of symptoms.
Because the virus becomes encoded within the genetic material of the host cell and is highly mutable, the problem of finding safe and effective therapies has been extremely difficult. Studies have attempted to determine the anti-HIV properties of many drugs, but the ethical and economic obstacles to clinical trials with experimental drugs are formidable. Given the immediacy of the epidemic, it is difficult to structure appropriate randomized clinical trials, which often take considerable time, to assess the safety and efficacy of a drug. Since the beginning of the epidemic, clinical research has refined the treatment of opportunistic infections.
In its first decade, AIDS created considerable suffering and generated an ongoing worldwide health crisis. During this brief period, the epidemic was identified and characterized epidemiologically, basic modes of transmission specified, a causal organism isolated, and effective tests for infection developed. In spite of this remarkable progress, which required the application of sophisticated epidemiological, clinical, and scientific research, the barriers to con-trolling AIDS are imposing and relate to the most complex biomedical and political questions. AIDS has already sorely tested the capabilities of research, clinical, and public-health institutions throughout the world.
Because HIV is related to other recently isolated primate retroviruses, such as simian T lymphotropic virus (STLV)-III in African green monkeys, many have speculated that HIV originated in Africa. Antibodies to HIV were discovered in stored blood dating back to 1959 in Zaire. According to experts, it is likely that HIV has existed for many years in isolated groups in central Africa. Because outside contacts were minimal, the virus rarely spread, and epidemics could not be sustained. Once a sizable reservoir of infection was established, however, HIV be-came pandemic. As with other sexually transmitted diseases, such as syphilis, no country wished the stigma of association with the virus’s origin.
The epidemic began at a moment of relative complacency, especially in the developed world, concerning epidemic infectious disease. Not since the influenza of 1918–20 had an epidemic appeared with such devastating potential. The developed world had experienced a health transition from infectious to chronic disease and had focused its resources and attention on systemic, noninfectious ailments. Thus, AIDS appeared at a historical moment comprising little social or political experience in confronting such a public-health crisis. The epidemic fractured a widely held belief in medical security.
Not surprisingly, early sociopolitical responses were characterized by denial. Initial theories, when few cases had been reported, centered on aspects of “fast-track” gay sexual culture that might explain the outbreak of immune-compromised men. Additional cases among blood recipients, however, soon led the U.S. Centers for Disease Control and prevention to the conclusion that an infectious agent was the likely link. Nevertheless, in the earliest years of the epidemic, few wished to con-front openly the possibility of spread beyond the specified “high-risk” groups. During this period, when government interest and funding lagged, grassroots organizations, especially in the homosexual community, were created to meet the growing need for education, counseling, patient services, and – in some instances – clinical research. Such groups worked to over-come the denial, prejudice, and bureaucratic inertia that limited governmental response.
As the nature and extent of the epidemic became clearer, however, hysteria sometimes replaced denial. Because the disease was powerfully associated with behaviors identified as immoral or illegal (or both), the stigma of those infected was heightened. Victims were often divided into categories: those who acquired their infections through transfusions or perinatally, the “innocent victims”; and those who engaged in high-risk, morally condemnable behaviors, the “guilty perpetrators” of disease. Since the early recognition of behavioral risks for infection, there has been a tendency to blame those who became infected through drug use or homosexuality, behaviors viewed as “voluntary.” Some religious groups in the United States and elsewhere saw the epidemic as an occasion to reiterate particular moral views about sexual behavior, drug use, sin, and disease. AIDS was viewed as “proof” of a certain moral order.
AIDS victims have been subjected to a range of discriminatory behavior, including loss of employment, housing, and insurance. Since the onset of the epidemic, violence against gays in the United States has increased. Despite the well-documented modes of HIV transmission, fears of casual transmission persist. In some communities, parents protested when HIV-infected schoolchildren were permitted to attend school. In one instance, a family with an HIV-infected child was driven from a town by the burning of their home.
By 1983, as potential ramifications of the epidemic became evident, national and inter-national scientific and public-health institutions began to mobilize. In the United States, congressional appropriations for research and education began to rise significantly. The National Academy of Sciences issued a consensus report on the epidemic in 1986. A presidential commission held public hearings and eventually issued a report calling for protection of AIDS sufferers against discrimination and a more extensive federal commitment to drug treatment. The World Health organization (WHO) established a Global Program on AIDS in 1986 to coordinate international efforts in epidemiological surveillance, education, prevention, and research.
Despite growing recognition of the epidemic’s significance, considerable debate continued over the most effective public-health responses. Although some nations – such as Cuba – experimented with programs mandating isolation of HIV-infected individuals, the World Health Organization lobbied against coercive measures. Given the lifelong nature of HIV infection, effective isolation would require life-time incarceration. With the available variety of less restrictive measures, most nations rejected quarantine as both unduly coercive and unlikely to achieve control. Traditional public-health approaches to communicable disease, including contact tracing and mandatory treatment, have less potential for control because no means exist to render an infected individual noninfectious.
Because biomedical technologies to prevent transmission appear to be some years away, the principal public-health approaches to con-trolling the pandemic rest on education and behavior modification. Heightened awareness of the dangers of unprotected anal intercourse among gay men, for example, has led to a significant decline in new infections among this population. Nevertheless, as many public-health officials have noted, encouraging the modification of risk behaviors, especially those relating to sexuality and drug abuse, presents no simple task, even in the face of a dread disease.
In the developing world, AIDS threatens to reverse recent advances in infant and child survival. The epidemic is likely to have a substantial impact on demographic patterns. Be-cause the disease principally affects young and middle-aged adults (ages 20–49), it has already had tragic social and cultural repercussions. Transmitted both horizontally (via sexual con-tact) and vertically (from mother to infant), it has the potential to depress the growth rate of human populations, especially in areas of the developing world. In this respect, the disease could destabilize the work force and depress lo-cal economies.
AIDS has clearly demonstrated the complex relationship of biological and behavioral forces in determining patterns of health and disease. Altering the course of the epidemic by human design has already proved to be no easy matter. The lifelong infectiousness of carriers; the private, biopsychosocial nature of sexual behavior and drug abuse; and the stigma already attached to those at greatest risk – all have made effective public policy intervention even more difficult. Finally, the very nature of the virus itself – its complex and mutagenic nature – makes a short-term technological breakthrough unlikely.
The remarkable progress in understanding AIDS is testimony to the sophistication of con-temporary bioscience; the epidemic, however, is also a sobering reminder of the limits of that science. Any historical assessment of the AIDS epidemic must be considered provisional.
Nevertheless, it is already clear that AIDS has forced us to confront a new set of biological imperatives.
By way of a caveat, recent estimates of the num-ber of HIV/AIDS infections, the competing theories of origin, conflicting interpretations of new evidence, and announcements of therapeutic and preventive progress are sometimes contradictory and thus constitute especially treacherous terrain.
Beginning with the estimates, in June of 1990 the WHO estimated that there were some 8 million HIV cases worldwide; the following year that estimate was raised to between 10 million and 12 million. Toward the end of the decade the WHO warned that the number of cases would reach between 20 million and 30 million cases by the year 2000. In retrospect, it seems that this estimate was much too conservative; by 1997 the number of cases already exceeded 30 million. By 2001, HIV had infected some 56 million individuals worldwide and killed more than 20 million of them. Left behind were an estimated 36 million living with HIV/AIDS and millions more expected to be-come infected in the early years of the twenty-first century.
Of the 30 million cases in 1997, almost 21 million were in sub-Saharan Africa alone (where in some places, such as Botswana, upwards of 36 percent of the adult population has become infected with HIV), while South and South-east Asia and the Pacific accounted for another 6 million cases. In all, the developing world contained 95 percent of the cases, and in 1998 it was estimated that 70 percent of all new infections and 80 percent of all AIDS deaths occurred in sub-Saharan Africa. By 2001, average life expectancy south of the Sahara had declined by 10 years and infant death rates had doubled. Illustrative of the impact of AIDS mortality is the example of Zambia, where a dire shortage of schoolteachers has developed because they are dying of AIDS faster than replacements can be trained.
In the United States – although the millions of cases of HIV infection that had been gloomily predicted by some did not materialize – 774,647 cases were reported between 1981 and 2001, and there were 448,060 deaths. By age and sex, the breakdown of those infected was 79 percent adult males, and by ethnicity 61 per-cent were black or Hispanic. The major avenues of transmission have been through male homosexual contact (48 percent) and intravenous drug abuse (26 percent), although HIV infection via heterosexual contact – generally be-tween infected males and uninfected females – is on the rise. Today the fastest growing groups of newly infected individuals are reported to be women and their children, and gay black males – the latter group accounting for 42 per-cent of all new infections. The U.S. cases are almost all HIV-1. Despite fears of HIV-2 also spreading in North America, only 64 cases have been documented, and these were all directly linked with West Africa.
Among HIV/AIDS researchers a consensus gradually emerged that simian immunodeficiency virus (SIV) had somehow managed to jump the species barrier from African primates (for whom it seems to be a relatively be-nign infection) to first infect humans in Cen-tral and West Africa and, somewhere along the line, became human immunodeficiency virus or HIV-1 and its subtypes (the most common form worldwide) and HIV-2.
Another question had to do with how the species barrier was hurdled. Again a consensus took shape; SIV had entered the blood of Africans engaged in chimpanzee butchering, after which it became HIV-1 (although the possibility of SIV evolving into HIV in the chimpanzee was not ruled out). Moreover, lineages of HIV transmitted by sooty mangabeys (also called the green monkey) were believed to have reached humans in like fashion to become HIV-2. Some, however, suspected that medicine had something to do with HIV becoming a human infection and, therefore, that AIDS had an iatrogenic or medical cause.
Initially, the WHO smallpox vaccination campaign in Africa from 1967 to 1980 came under scrutiny for the possibility that HIV had been propelled through countless bodies with the repeated use of inadequately sterilized needles, or even that the vaccine had been contaminated. These hypotheses, of course, dealt with HIV transmission and did not really confront the question of its origin. Another hypothesis, however, did – this one focusing on the polio vaccination campaign conducted in Africa (and elsewhere) during the late 1950s. In the (then Belgian) Congo, chimpanzee kidneys were used to culture the poliovirus, which in turn, it was argued, could have contaminated the oral polio vaccine used in a widespread vaccination effort during 1957–58. Buttressing the case was that this region subsequently became the major epi-center of the burgeoning AIDS epidemic. Also bolstering it was the announcement in 1999 by a group of University of Alabama researchers that they had determined that a kind of chimpanzee once common in West Africa was indeed the source of HIV.
Yet other recent evidence was not so support-ive. Most recently, in 2001, it was announced that a vial of the suspected polio vaccine had been found and that analysis had revealed no trace of HIV. Moreover, a study published in 2000 in Science had already cast considerable doubt on the contaminated vaccine hypothesis by showing that HIV-1 may well have been present in human African populations since at least the 1930s – almost 30 years before the polio vaccination campaign in the Congo. That date, however, is for the time that the HIV-1 group of viruses began to diversify, and not for when they were transmitted to humans. Thus, vital questions of transmission and origin re-main unresolved – that of origin because even if chimpanzees did pass on HIV to humans, they may also have been infected from yet another source.
Great strides have been made recently toward the goals of treatment and prevention. In 1986, the drug azidothymidine (AZT) was shown to extend the period of latency for AIDS. It is one of five drugs called nucleosides licensed by the U.S. Food and Drug Administration, all of which are inhibitors of the viral enzyme reverse transcriptase (RT), which performs reverse transcription – the conversion of RNA into DNA that HIV must undergo to be infec-tive. In the second half of the 1990s, protease inhibitors (which cripple a viral enzyme vital to HIV reproduction) came into use and two nu-cleoside inhibitors and one protease inhibitor were blended together into what was called the “antiviral cocktail.” The results were miraculous. Individuals on the verge of death were going back to jobs and resuming normal lives, the mortality rate from AIDS in the United States fell dramatically, and it seemed that a major battle against the disease had been won.
But it was an incomplete victory, because the “cocktail” can produce unpleasant side effects, and just one missed dose can give the virus the opportunity to quickly mutate into a strain that resists the drugs. In fact, drug-resistant strains of HIV are already complicating AIDS treatment, which has led to different combinations of “cocktail” ingredients, each of which interferes with certain steps in the HIV infection process. Still other drugs have been brought effectively to bear on some of the “killer” opportunistic infections such as pneumocystis pneumonia and tuberculosis, which are the principal cause of AIDS deaths worldwide. But whether the miracle will continue indefinitely remains to be seen. The therapy is new and consequently the long-term success rate is unknown. More-over, a per-patient annual cost of some 10,000– 12,000 U.S. dollars limits this costly drug treatment to a relatively few victims in the developed world. Thus far, pressure on pharmaceutical manufacturers to make low- or no-cost drugs available to the developing world’s mil-lions stricken with HIV/AIDS has produced little in the way of results.
Work is also being done to develop a vaccine that could be both protective by preventing infection and therapeutic for those infected, by prolonging survival and decreasing immune system destruction. At the turn of the twenty-first century, vaccines were being tested that had proven effective in protecting monkeys from HIV, and large-scale trials were under way to test them for human safety. In addition, Merck and Company, with its enormous re-sources, announced in 1999 that it would begin human trials on two vaccines. However, provided that a safe vaccine does become available, the problems of administering it – especially to the millions at high risk in the developing world – are daunting because it appears that one primary injection will be required, followed by three booster shots. The good news, of course, is that the question seems no longer to be whether there will be a vaccine, but rather when a vaccine will be available.
Moreover, gene therapy holds out promise of inhibiting HIV by introducing a gene into cells that interferes with the viral regulatory proteins, or even one that will protect cells from HIV infection. But all of these measures, even when they do bear fruit, will probably be too late to stop AIDS from becoming the biggest killer-disease in human history.