HUMAN IMMUNODEFICIENCY VIRUS

Human Immunodeficiency Virus (HIV) is usually spread unintentionally, but in the course of sexual or drug-using conduct that is intentional. Since the beginning of the HIV epidemic, criminal law has been proposed, and sporadically deployed, as a means of addressing conduct that exposes others to, or actually infects them with, HIV. This entry surveys the practical, legal, and social issues that arise in the "criminalization" of a public health threat.

The case for criminalizing conduct that spreads HIV is straightforward. People who deliberately or recklessly expose others to or actually infect others with HIV are said to deserve punishment. Such punishment might have the added benefit of deterring others from creating the same risks. Criminal laws certainly express society's disapproval of the conduct, which may provide additional deterrence through social influence. In practice, however, the issue is much more complicated.

Criminalization as a health measure

The public health case for criminalization is weak. Criminal law can be an effective tool of HIV prevention only if it incapacitates or deters the people whose behavior is responsible for a significant proportion of new cases, but criminalization stumbles almost immediately on a paradox. The behavior most widely accepted as wrong—deliberately using HIV as a tool to harm or terrorize another—is too rare to influence the epidemic, whereas the behavior most responsible for spreading the virus—voluntary sex and needle sharing—is difficult and controversial to prohibit. Both the impetus for and opposition to criminalization reflect profound social differences over the acceptability of homosexuality and drug use, and the clash of values those differences entail.

Sex and needle sharing as crime

In principle, a zone of wrongful exposure to HIV can be delineated in terms of autonomy. The risk of HIV transmission through sex is low enough that a person may reasonably choose to run it, but high enough that no one should endanger another without consent. The consent principle embraces the worst cases of deliberate exposure, rape, and fraud, but also the common sexual encounters (or needle sharing) that drive the epidemic. Research indicates that many people who know they are infected with HIV sometimes engage in unsafe sexual or drug-using behavior without informing their partners of their infection. Women, with less power than their male partners, are particularly vulnerable to unwanted sexual risk.

Although most people would probably agree that concealment of one's HIV status from a sex or needle partner is wrong, there are both principled and practical objections to enforcing the norm through criminal law. Sex and drug use are voluntary activities with known (and rather moderate) risks. They are normally conducted under implicit social conventions concerning disclosure, risk-taking, and consent that may not require explicit discussion of infection. Some contend, on libertarian or privacy grounds, that the government simply ought not to be regulating such behavior. Other commentators suggest that sexual interaction is simply too psychologically complicated and socially unsettling to be sensibly analyzed in the terms of culpability offered by criminal law.

Public health professionals have worried that designating such common behavior as criminal could add to the stigma and social risk of getting tested, educated, or treated. They fear that prosecutions, particularly if they involve use of public health records to document prior knowledge of infection, can rend the fabric of privacy and cooperation necessary to effective prevention. Although empirical support for this concern is weak, even a minor negative effect would outweigh the negligible benefits of criminalization for public health.

Research has largely discredited the belief that needle sharing is a social preference in favor of the view that it is a response to the scarcity of new, sterile injection equipment. This scarcity, in turn, is attributable to drug paraphernalia and needle prescription laws designed to prevent drug users from obtaining injection equipment. It is objectionable on principle, as well as counterproductive from a public health perspective, to deliberately prevent individuals from getting sterile syringes while prosecuting those same people for sharing unsterile ones.

Mistrust is the greatest obstacle to criminal law's protection of sexual autonomy and public health. Many people are dubious of the motivation behind criminalization. Many gay men, for example, fear that HIV is used as an excuse to suppress gay sexuality. Moreover, the fact that criminalization initiatives tend to come from more conservative legislators, and are never systematically enforced, fuels suspicion that criminalization is really part of a larger struggle between social factions for normative dominance in matters of sexuality. Sexually-transmitted disease control policies have historically reflected and been a vehicle for the expression of competing social norms about sexual behavior and the status of women and minorities. On this view, criminalization of HIV is of a piece with laws prohibiting sodomy, or denying civil rights protection to gay men and lesbians.

The behavioral impact of criminalization

The population of people spreading HIV is so large, and the resources devoted to detecting and prosecuting exposure crimes so small, that incapacitation can be ruled out as a plausible outcome of current criminalization initiatives. Deterrence is notoriously difficult to assess, but on each of the leading theories of the mechanism of deterrence the suggestion that criminalization will deter people from having sex or sharing needles without disclosure is implausible.

Rational actor theories posit that deterrence rests on some combination of likelihood of detection and severity of punishment. Long imprisonment is a severe punishment for a person with HIV, whose life expectancy is shorter than usual and whose need for the best medical care is greater. The chances of being prosecuted, however, are so low as to undermine the impact of a severe sanction.

Legitimacy-based theories suggest that people may obey the law because they believe it is right to do so, and in particular because they believe that the legal system operates fairly in setting and enforcing norms. The small number of prosecutions tends by itself to make any one appear freakish or arbitrary. More importantly, the criminalization of HIV entails the imposition of disputed norms of sobriety and chastity upon communities that have substantially defined themselves in their rejection or subversion of the values of the dominant groups in society. It seems unlikely that gay men or drug users will change their behavior out of respect for authority.

Criminalization in practice

Prosecutors began charging people with HIV-related crimes early in the epidemic. Nearly all cases involved exposure to the virus, rather than its actual transmission. As many as one hundred prosecutions had been initiated by 1988, when the first reported decisions appeared. In that same year, the final report of the Presidential Commission on HIV recommended that "HIV infected individuals who knowingly conduct themselves in ways that pose significant risk of transmission to others must be held accountable for their actions." By 1999, there were approximately fifty reported cases and at least 200 prosecutions. Thirty states had passed HIV-specific criminal provisions, laws that varied enormously in the conduct they embraced and the penalties they imposed.

The cases fall into three main groups. The most numerous is comprised of instances of the allegedly deliberate use of HIV as a weapon to cause emotional distress or bodily harm. These cases, which have commonly involved biting or spitting, are notable for the high charges (including attempted murder) and long sentences meted out. A smaller group is made up of cases using HIV as a basis for more severe sentencing in cases of prostitution, rape, and child abuse. The third group is comprised of prosecutions, under the Uniform Code of Military Justice, of military personnel who disobeyed "safe-sex" orders to refrain from sexual contact without informing partners of their infection. No more than a handful of civilians have been prosecuted for isolated instances of unsafe sex without disclosure, and no reported cases involve needle sharing.

General criminal law

Depending on the actor's state of mind, actual transmission of HIV by any means could be prosecuted as murder or manslaughter if it resulted in death of the exposed party. In practice, the long latency period of the disease, and old doctrines such as the rule that the fatal act must have occurred within a year and a day of the death to be prosecuted as a murder, may help explain why there is no reported case in the United States.

More commonly prosecuted is the act of exposing someone else to HIV. Available charges include reckless endangerment, assault, assault with a deadly weapon (or aggravated assault), and attempted murder. Reckless endangerment requires proof that the actor placed another at risk of serious bodily harm with conscious disregard of the risk. An assault is established if the actor is proven to have knowingly or purposefully engaged in conduct likely to transmit HIV. Some courts have allowed prosecution for aggravated assault or assault with a deadly weapon on the theory that HIV, or some body part containing HIV, is a weapon. Attempted murder requires a showing that the defendant purposely or knowingly deployed HIV as a weapon of homicide.

Both proponents and opponents of criminalization have been critical of the current approach of the criminal law to HIV cases. Proponents worry that bad actors get off too easily. The long course of the disease makes prosecuting actual transmission as murder impractical. Cases of exposure are also said to be hard to prosecute. A minority of courts have refused to analogize HIV to a deadly weapon, or have ruled that one or two sexual contacts are simply not risky enough to place another at the kind of risk prohibited by assault. Numerous commentators have pointed to a supposed difficulty of proving an intent to harm, particularly where, as the Supreme Court of Maryland ruled, proof of infection alone is not sufficient to establish the defendant's intent to do harm.

Critics worry that both intent and risk are poor tools for assessing HIV cases. They note convictions in numerous assault and attempted murder cases involving very low risk acts like spitting, biting, and throwing infected body fluids. In such cases, and potentially in cases involving voluntary sexual activity, the unacceptability of the risk to jurors can skew their assessment of the likelihood of harm. Critics also worry about the effect of race, class, and the stigma of HIV on the decision-maker's assessment of the defendant's intent. Convictions of biters and spitters for attempted murder are seen as proof that judges and juries can ascribe a homicidal intent to a person with HIV even where the chosen weapon was practically incapable of causing death.

HIV-specific offenses

Concerns about the inappositeness of general criminal law has long led commentators from across the spectrum of opinion to prefer laws specifically defining culpable conduct among people with HIV, but positive legislation has brought neither clarity nor consistency. Many statutes deal only with specific modes of risk creation, such as blood donation or prostitution. Those that address sexual behavior more generally vary in the state of mind and acts addressed, as well as on important issues such as whether condom use or other safe sex practices can be considered in defense.

Two examples illustrate the range of provisions. California's law, one of the narrowest, covers only unprotected sexual activity carried out with the specific intent to infect the other, and states that knowledge of infection alone is not sufficient to satisfy the intent requirement. Idaho's law covers any transfer or attempted transfer of any body fluid, body tissue, or organ to another by a person who knows of his or her infection or any symptom of infection. "Transfer" includes "engaging in sexual activity by genital-genital contact, oral-genital contact, analgenital contact," without regard to the riskiness of the act or even the use of a condom. Thus in Idaho, a person who has oral sex using a condom but without informing the other is liable to up to fifteen years in prison, whereas the same conduct is not covered by California's law at all. Even without the condom and with a specific intent to infect, such conduct in California would be subject to a maximum of eight years. Absent systematic enforcement, the few prosecutions under these laws have depended upon a happenstance of detection under circumstances that led a prosecutor to charge the crime.

The "extreme case"

Criminalization debate tends to be framed in terms of "willful" or "incorrigible" people who expose large numbers of partners to their infection. An example is NuShawn Williams, who had sex with dozens of women, many of them minors, after being told he was infected. Thirteen of the women were later found to have HIV. Mr. Williams, who is black, claimed to believe that white health officials had falsely told him he was HIV infected in order to discourage him from having sex with white women in the rural area where he was diagnosed. He denied any wish to hurt any of this partners. After public health authorities released his name, he was discovered in a New York City jail. He eventually pled guilty to charges of statutory rape and reckless endangerment and was sentenced to between four and eighteen years in prison.

Proponents of criminalization tend to point to his as the "easy" case: a man, tested and counseled, continues to have sex and infect underage partners with a conscious disregard of the risk. The biggest problem with his case was that he could not be charged with more serious crimes: none of his victims had died, or were likely to predecease Williams himself, while prosecutors in New York reportedly doubted they could prove he had the specific intent to kill required to make out the offense of attempted murder.

If one accepts that he believed he was infected and understood the risks, then perhaps Williams's was an easy case. But this, opponents suggest, is just the problem: Williams's demonic intent was assumed, not proven. For example, his ability to recall the names of most of his partners when questioned by health authorities, which could reasonably be read as proof of fondness and concern, was interpreted by more than one commentator as malignant sexual score-keeping. For criminalization critics, it is Williams's race, class, and incongruity with his rural setting that made him the "easy" case, and not a basic difference between him and other infected people.

Conclusion

Public health programs prevent HIV through the systematic deployment of interventions designed to change the behaviors that pose the highest risk to the population. Although criminal law is sometimes a useful public health tool, as against HIV it has been applied to a small number of randomly identified cases to punish and deter wrongdoing through action taken against individuals deemed morally culpable. Neither theory nor experience supports the belief that criminal penalties can reduce the rate of HIV's spread.

Scott Burris

See also Assault and Battery; Attempt; Fear of Crime; Homosexuality and Crime; Political Process and Crime; Rape: Legal Aspects.

BIBLIOGRAPHY

Brandt, Allen M. No Magic Bullet: A Social History of Venereal Disease in the United States Since 1980. New York: Oxford University Press, 1987.

Burris, Scott; Dalton, Harlon; and Miller, Judith, eds. AIDS Law Today: A New Guide for the Public. New Haven, Conn.: Yale University Press, 1993.

Dangerous Bedfellows, eds. Policing Public Sex: Queer Politics and the Future of AIDS Activism. Boston, Mass.: South End Press, 1996.

Gostin, Lawrence O., and Lazzarini, Zita. "Prevention of HIV/AIDS among Injection Drug Users: The Theory and Science of Public Health and Criminal Justice Approaches to Disease Prevention." Emory Law Journal 46 (1997): 587–696.

Gusfield, Joseph R. Symbolic Crusade: Status Politics and the American Temperance Movement. Urbana, Ill.: University of Illinois Press, 1963.

Mark, Gary; Burris, Scott; and Peterman, Thomas. "Reducing Sexual Transmission of HIV from Those Who Know They Are Infected: The Need for Personal and Collective Responsibility." AIDS 13 (1999): 297–306.

Stephens, Alan. "Annotation: Transmission or Risk of Transmission of Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome as Basis for Prosecution or Sentencing in Criminal or Military Discipline Case." American Law Reports 5, vol. 13 (1993): 628–683.

Sullivan, Kathleen M., and Field, Martha A. "AIDS and the Coercive Power of the State." Harvard Civil Rights –Civil Liberties Law Review 23 (1988): 139–197.

HIV

THE DISCOVERY OF HIV

TESTING FOR HIV

TREATMENT AND PREVENTION

THE STIGMA OF AIDS

BIBLIOGRAPHY

The human immunodeficiency virus (HIV) is part of a family of retroviruses that have the capacity of reproduction from RNA in the nucleus of a helping cell of the human immune system. Using enzymes—chemical substances in the human organism that enhance reactions without intervening in them—the virus breaks through the cell membrane to the nucleus, where it is reproduced. Infection with HIV leads to the disease known as AIDS.

The origin of HIV is unknown, but it is widely understood that it is a mutation of a similar retrovirus, such as the simian immunodeficiency virus. It is speculated that the virus developed the capacity to infect human beings through the practice of ingesting raw meat or blood in religious rituals in isolated parts of Africa. Even though the first AIDS cases were reported in Africa in the early 1980s, several known cases were before this date.

THE DISCOVERY OF HIV

At the beginning of the AIDS epidemic, the virus was initially called human T-lymphotropic virus type III (HTLV III) by the U.S. research group under the leadership of Robert Gallo. The virus was also discovered at about the same time by researchers at the Pasteur Institute of France under the leadership of Luc Montagnier, who named it lymphadenopathy-associated virus (LAV). Following an international controversy between the two researchers, who both claimed credit for the discovery, the name HIV was agreed upon.

By 1982 it had been established that HIV had caused the destruction of the immune system of numerous individuals, rendering them susceptible to infections that produced a combination of diseases, such as Kaposi sarcoma and pneumonia. This overall disease process was called acquired immunodeficiency syndrome (AIDS). By this time it had also been established that the virus was transmitted via body fluids, such as blood and semen.

A number of factors—including the migration of infected people to populated zones, overpopulation in certain communities, difficulties in access to medical care, and ignorance of the disease—led to the infection becoming a pandemic by the end of the 1980s. The first AIDS cases in the United States were reported in the summer of 1980, when the Centers for Disease Control and Prevention (CDC) reported several cases of young males with opportunistic infections and a compromised immune system. The number of reported AIDS cases then began to increase in a geometrical way through the entire world. According to the CDC, the cumulative estimated number of diagnoses of AIDS through 2003 in the United States was 929, 985. Adult and adolescent AIDS cases totaled 920, 566, with 749, 887 cases in males and 170, 679 cases in females. The remaining 9, 419 cases had occurred in children under age 13. At the end of 2003, it was estimated that 1, 039, 000 to 1, 185, 000 persons in the United States were living with HIV/AIDS and that between 24 and 27 percent were undiagnosed and unaware of their condition.

TESTING FOR HIV

There is a test to detect the presence of HIV antibodies. A more specialized test, the polymerase chain reaction (PCR) test, can identify the virus, but it is only used for special cases or research due to its high cost. For the general public, the ELISA test is used, which only detects the presence of HIV antibodies. This test is highly sensitive for negatives, which is why it is commonly used for screening possible cases. But because of this sensitivity, ELISA tests that are positive must be confirmed with a more accurate test, called the Western blot. Both tests are readily available through public health services, and many health community-based organizations provide the test at outreach activities in the communities.

TREATMENT AND PREVENTION

As of 2007 there was no available vaccine for HIV. More than 95 percent of all new infections were in developing countries, making HIV/AIDS one of the most serious threats to global health and global development. Many believe that only a vaccine will stop the spread of the infection. Developing a vaccine will thus represent a huge milestone in the AIDS epidemic, and several clinical trials are being developed in different countries. However, the versatility of the virus and other concerns have made this a difficult task.

Due to the nature of HIV infection and the lack of a cure or vaccine, the only way to address the epidemic is by means of prevention. Primary prevention programs target vulnerable populations by means of culturally and competent interventions designed to help people avoid being infected. Because the virus is transmitted by contact with fluids, sharing infected needles for drug use, having sexual intercourse without protection, and mother-to-infant transmission are the main venues for the virus to be introduced to human beings. Important primary prevention interventions have been developed and evaluated in the United States and other industrialized countries, and these are being transferred to other communities around the world. These prevention programs include education about the virus, condom distribution, clean needle distribution for drug addicts, and peer counseling, and they have slowed the spread of HIV. The basic idea is that by learning the ways the virus is transmitted and by developing personal and social skills that protect and empower atrisk minority communities, it is possible to stop the spread of the infection.

Advances in treatment have yielded important new AIDS therapies, but the cost and complexity of their use put them out of reach for most people in the countries where they are needed the most. In industrialized nations, where the drugs are more readily available, side effects and increased rates of viral resistance have raised concerns about the long-term use of these therapies. Since the mid-1990s, HIV infection has spread most rapidly among women, children, and sexual minorities. Both in the United States and in developing countries, the incidence of HIV infection has had a disproportional impact on communities of color. Efforts at primary prevention must therefore take into consideration the social and cultural context and meanings of what are known as “high-risk behaviors.”

It is also important of course to pay attention to those already living with HIV/AIDS, with the goal of providing them access to care and secondary prevention. By engaging people living with HIV/AIDS in appropriate treatment, the quality of life of these individuals can be enhanced. This level of treatment will also reduce the continuing transmission of the infection. For this to happen, the human rights of people living with HIV/AIDS need to be protected. This will encourage them to get tested and receive medical and social care.

THE STIGMA OF AIDS

Jonathan Mann, the founding director of the World Health Organization’s Global Programme on AIDS, described the HIV epidemic as more than just a biological disease. It is also a social phenomenon that he identified as potentially explosive because it is an epidemic of social, cultural, economic, and political responses to the disease. This social epidemic is characterized above all by exceptionally high levels of stigma, discrimination, and at times collective denial.

The concept of stigma dates to ancient Greece, where it was used to describe persons who had been involved with certain bad deeds, for which they were distinguished from others by the application of bodily marks or tattoos. People so marked were to be avoided by the general populace. The concept has also been associated with an unnatural mark in the bodies of saints, a mark made with a hot iron on the flesh of slaves, a bad reputation, and even a physical dysfunction. Some authors have described stigma as a social construction associated with the recognition of a “difference” based on a specific characteristic, which is used to devalue the person who possesses that characteristic. All of these definitions share the idea that a stigma is the negative evaluation of a particular difference that may be identified in a person. The stigma associated with AIDS has become the biggest obstacle for HIV/AIDS prevention, because it hinders the possibility of dignity and access to care for people living with the infection.

SEE ALSO AIDS; AIDS/HIV in Developing Countries, Impact of; Disease; Public Health; World Health Organization

BIBLIOGRAPHY

Centers for Disease Control and Prevention. 1981. Kaposi’s Sarcoma and Pneumocystis Pneumonia among Homosexual Men: New York City and California. Morbidity and Mortality Weekly Reports 30: 305–308.

Centers for Disease Control and Prevention. 1981. Pneumocystis Pneumonia: Los Angeles. Morbidity and Mortality Weekly Reports 30: 250–252.

Centers for Disease Control and Prevention. 2004. HIV/AIDS Surveillance Report. Vol. 15, Cases of HIV Infection and AIDS in the United States, 2003. Atlanta, GA: Author.

Goffman, Erving. 1963. Stigma: Notes on the Management of Spoiled Identity. Englewood Cliffs, NJ: Prentice-Hall.

Herek, Gregory M. 1999. AIDS and Stigma in the United States. American Behavioral Scientist 42 (7): 1106–1116.

Herek, Gregory M., and John P. Capitano. 1999. AIDS Stigma and Sexual Prejudice. American Behavioral Scientists 42 (7): 1130–1147.

HIV Vaccine Trials Network. “The Step Study”: HVTN 502/Merck 023 A Merck/HVTN Proof-of-Concept Vaccine Trial. http://www.hvtn.org/science/step.html.

Joint United Nations Programme on HIV/AIDS (UNAIDS). 2003. Report on the Global HIV/AIDS Epidemic, December 2003. Geneva, Switzerland: UNAIDS.

Kalichman, Seth C. 1998. Understanding AIDS: Advances in Research and Treatment. Washington, DC: American Psychological Association.

José Toro-Alfonso

HIV/AIDS

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has reached pandemic proportions and has presented a multiple-dimension challenge for science, technology, and ethics. In 2004 approximately 39.4 million people worldwide were infected with HIV/AIDS, among whom about 3.1 million died in that year, including about 510,000 children under age fifteen. The Joint United Nations Programme on HIV/AIDS/World Health Organization (UNAIDS/WHO) estimates that in that year 4.9 million new infections occurred. Impacts have been more severe in southern Africa, where about one-third of the deaths occurred in 2004 and where life expectancies have dropped by more than 20 years in some countries. HIV/AIDS increasingly affects women and children; nearly half of those infected worldwide are female, with even higher infection rates for women in Africa. Infected pregnant and nursing women can pass the disease to their babies.

Between 2001 and 2004 global funding for HIV/AIDS relief tripled to $6.1 billion, with resultant improvements in treatments and services; this figure includes estimates of funding from all sources, ranging from individuals and families to national and international efforts. Like infections, however, services are unevenly distributed, with the poor and stigmatized remaining underserved. Analyzing the ethics and politics of scientific, technological, and other responses is a contentious issue.

Historical Perspectives

It is useful to compare the HIV/AIDS pandemic with the Spanish influenza epidemic of 1917–1918, which also was promoted by the global transportation network at an earlier stage of its evolution. In a little less than two years the Spanish flu is estimated to have killed from 21 to 50 million persons worldwide in a population of approximately 1.8 billion. While HIV/AIDS has not yet killed as large a percentage of the world's population as the Spanish influenza epidemic, HIV/AIDS infections are not self-limiting and infection rates are expected to remain high unless effective prevention programs are developed and implemented.

Mirko Grmek (1990) provides an extensive history of the emergence and identification of HIV/AIDS. In the late 1970s the disease began to appear in the United States and Europe as physicians noticed unusual symptoms in members of homosexual communities in California and New York. Those patients presented with a variety of symptoms, such as pneumonia, mononucleosis, thrush, and Kaposi's sarcoma. Some were relative benign conditions, yet the patients went into a rapid decline, and their immune systems appeared to be compromised. The U.S. Centers for Disease Control announced the disease on June 5, 1981, but the disease was not named acquired immunodeficiency syndrome until the summer of 1982. Most of the early cases involved homosexuals, but other cases developed in intravenous drug users and then in heterosexual males, women, and patients with no history of drug use. The disease eventually was recognized in equatorial Africa, where cases might have appeared as early as 1962.

Scientists eventually identified "Patient Zero," a flight attendant who apparently was responsible for infecting a large number of the early patients in the United States. Spread of the disease thus took advantage of a global transportation network, establishing a pattern that was repeated on a much less dramatic scale with the severe acute respiratory syndrome (SARS) in 2002–2003 and poses an ongoing challenge to world health management. Patient Zero continued to engage in unprotected sexual activity long after being diagnosed, posing questions about responsibility to both patients and the medical community.

Science, Technology, and Responsibility

Since the early 1980s scientific research on HIV/AIDS has been involved in a series of controversies. For instance, immediately after the identification of AIDS researchers began to try to identify the cause. Priority in the 1983 identification of HIV as the infectious agent was claimed by both Robert Gallo at the National Cancer Institute in the United States and Luc Montagnier at the Institut Pasteur in France in what became a widely reported case of questionable scientific conduct. Even after the discovery of HIV a prominent researcher, Peter Duisberg, rejected it as the basic cause of AIDS and was accused of scientific irresponsibility.

HIV/AIDS research has divided scientists and has caused conflicts between scientists and the public about research strategies and priorities. Should the emphasis be on basic immunological science or on clinical treatments? Should treatment research be aimed at preventing human cell infection by HIV or attacking human cells that already are infected? More generally, what are the relative costs and benefits of spending money on HIV/AIDS research instead of on research into another disease, such as malaria or diarrhea? An estimated 300 million people are infected with malaria, among whom 1 to 1.5 million die annually. A fraction of the money spent on HIV/AIDS research and treatment would have a much greater impact on malaria, and the provision of safe supplies of public drinking water would cause a significant reduction in the over 1 million deaths each year from diarrhea.

Research, particularly drug testing, triggers further ethical questions. How much testing should be conducted before a potentially lifesaving drug is made available to the public? What rules apply when scientists conduct research in developing countries: the rules of the corporate home nation or the rules in the country where research is conducted? Are some policies, such as informed consent, so basic that they should apply anywhere in the world? Does consent always attach to the individual, or does it extend in some cases to communities with high infection rates? Should subjects and their communities participate in research design? How can information about research be explained effectively to people who are not familiar with scientific research and its implications? Can effective treatment be withheld for the purpose of advancing scientific understanding and the possibility of developing new drugs? How can participants be protected from or compensated for negative unintended consequences of research trials? What obligations do researchers have to provide short- and long-term health care to research subjects and their communities? How should societal needs for research be balanced against the rights of the individual? Vaccine research poses special problems because the subjects subsequently may test positive for HIV/AIDS.

Debate also continues over the relative merits of treatment and prevention. Is it better to ease suffering and prolong the lives of those already infected or to prevent new cases from occurring? Prevention will help only those who are not currently living with HIV/AIDS, whereas treatment is needed for the millions already infected to prolong lives, maintain family incomes, and promote general economic stability. Moreover, infected patients need relief from suffering

in addition to treatment to slow the progress of the disease. Should scarce human and financial resources be diverted from prevention and treatment to provide palliative care?

Additionally, some people see HIV/AIDS primarily as a behavioral problem; if the behavior changes, the problem will disappear. Controlling HIV/AIDS is about more than developing drugs and vaccines; social science also plays an important role. New drugs will not reach patients unless medical services and drug delivery systems in poor countries are improved. The public must be educated about both causes and treatment. Researchers should investigate reasons for stigma and develop strategies to reduce discrimination and protect the most vulnerable. Within the prevention camp some advocate abstinence as the only moral alternative, whereas others recognize the reality of sexual activity and believe it is more ethical to promote condom use to reduce infection. In such a complex scientific and technology context what is the proper mix of prevention, treatment, and care?

Social Responsibilities

The infectious nature of HIV/AIDS also raises questions about societal responsibilities to potential victims. Should doctors or health institutions inform others when a patient is diagnosed with HIV/AIDS? How should the need to prevent the spread of a deadly disease be balanced against a patient's right to privacy? Women may be particularly at risk from identification because their subordinate status in many places may subject them to social isolation or deprivation of home or property.

Society often discriminates against people infected with HIV/AIDS. Discrimination may be driven by fear of infection, and education should be provided so that people know that the disease is not spread through casual contact. The general stigma attached to homosexuals, drug users, and the poor also drives discrimination. UNAIDS attributes the lack of political will to deal with the pandemic in part to the high infection rates among "marginalized and stigmatized population groups such as women who sell sex, drug injectors and men who have sex with men."

HIV/AIDS exacerbates gender inequities. Women often lack both information about the disease and the power to refuse sex or demand that their sexual partners use condoms. Identification of affected women puts them at higher risk of stigmatization, expulsion from their families, and deprivation of property and employment. Poor women who lose their spouses to the disease may be unable to support their families. More than 2 million children are infected with HIV/AIDS. Millions of others live with infected family members or have been orphaned by the pandemic.

Earlier in the epidemic the high incidence of HIV/AIDS among American gay males juxtaposed prejudice against homosexuals with the increasing political influence of affluent gay men. The gay community effectively concentrated attention on the emerging disease; that resulted in the allocation of research dollars to develop new treatments. HIV/AIDS is now relatively controllable for those who can afford expensive antiretroviral treatments, but the epidemic continues to spiral out of control because millions of infected poor people cannot afford treatment. The needed antiretrovirals are too expensive for most HIV/AIDS patients, and 90 percent of those who need drugs cannot afford them; most of those patients live in sub-Saharan Africa.

Some countries, such as Brazil, have made antiretroviral drugs available for free or at low cost to poor people who need them. Such programs help current patients but may reduce incentives for future pharmaceutical research. Drug companies engage in research and development to make money; if developing countries can obtain drugs without paying market prices, profits will fall and pharmaceutical companies may be less likely to do research into diseases that occur primarily among the poor. Nevertheless, the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) allows an exception to intellectual property rights in special cases such as emergencies, and that provision has been used to give developing countries access to HIV/AIDS drugs.

Michael Specter maintains that treatment is not enough; only a vaccine can stem the pandemic, yet drug companies lack sufficient incentives to develop a vaccine. This constitutes a case of market failure requiring government intervention.

Pharmaceutical companies in affluent industrialized countries conduct most research on new drugs and vaccines. Do they have a corporate responsibility to spend money on public health problems that may not produce profits? Do their countries have a responsibility to protect the less developed world by providing direct assistance or incentives for drug research? The developed world may have a direct stake in stopping the pandemic to reduce economic and political destabilization in many poor countries.

HIV/AIDS constitutes a global health crisis, but those in greatest need of assistance live in the poorest countries or are among the poorest and most stigmatized members of more affluent societies and lack strong political support. The crisis affects more than individuals; families are disrupted, and societies destabilized: "AIDS is accomplishing a sweeping undoing of past human development advances, especially in southern Africa". The HIV/AIDS pandemic requires strategies to address problems from the individual level to the international level.

MARILYN AVERILL

SEE ALSO African Perspectives: HIV/AIDS;Drugs;Emergent Infectious Diseases;Health and Disease;Medical Ethics.

BIBLIOGRAPHY

Attaran, Amir, and Jeffrey Sachs. (2001). "Defining and Refining International Donor Support for Combating the AIDS Pandemic." Lancet 357: 57.

Feenberg, Andrew. (1995). Alternative Modernity: The Technical Turn in Philosophy and Social Theory. Berkeley: University of California Press.

Grmek, Mirko D. (1990). History of AIDS: Emergence and Origin of a Modern Pandemic. Princeton, NJ: Princeton University Press. This book presents a detailed history of the HIV/AIDS pandemic and attempts to identify the emerging disease and considers both biological and social factors contributing to the pandemic.

The Global Aids Policy Coalition. (1992). AIDS in the World: A Global Report. Mann, Jonathan M., general editor; Tarantola, Daniel J. M., scientific editor; Netter, Thomas W., managing editor. Cambridge, MA: Harvard University Press, 1992). This comprehensive book provides detailed chapters on "The Impact of the Epidemic," "The Global Response," "Global Vulnerability," and "Critical Issues."

Marais, Hein, et al. (2004). AIDS Epidemic Update: 2004. Geneva: UNAIDS. The UNAIDS/WHO web site provides one of the most comprehensive sources for current information about HIV/AIDS and international responses to the pandemic.

Specter, Michael. (2003). "The Vaccine: Has the Race to Save Africa from AIDS Put Western Science at Odds with Western Ethics?" New Yorker, February 3.

INTERNET RESOURCE

Wolf, Leslie E., and Bernard Lo. (2001). "Ethical Dimensions of HIV/AIDS." HIV Insite. Available from http://hivinsite.ucsf.edu/InSite?page=kb-08-01-05.

HIV

HIV, the human immunodeficiency virus, is the virus that causes AIDS, a debilitating and deadly disease of the human immune system. HIV is one of the world's most serious health problems: at the end of 2001, more than 40 million people worldwide were infected with HIV and living with the virus or AIDS. The World Health Organization estimates that about 20 million people have died from AIDS since the infection was first described in 1981. Nearly 500,000 of those deaths have occurred in the United States. Although there is no cure for the disease, therapies exist that reduce the symptoms of AIDS and can extend the life spans of HIV-infected individuals. Researchers are also pursuing protective vaccines, but a reliable vaccine might still require years to develop.

HIV and AIDS

HIV infects certain cells and tissues of the human immune system and takes them out of commission, rendering a person susceptible to a variety of infections and cancers. These infections are caused by so-called opportunistic agents, pathogens that take advantage of the compromised immune system but that would be unable to cause infection in people with a healthy immune system. Rare cancers such as Kaposi's sarcoma also take hold in HIV-infected individuals. The collection of diseases that arise because of HIV infection is called acquired immune deficiency syndrome, or AIDS. HIV is classified as a lentivirus ("lenti" means "slow") because the virus takes a long time to produce symptoms in an infected individual.

HIV Life Cycle: Entering Cells

Like a typical virus, HIV infects a cell and appropriates the host's cellular components and machinery to make many copies of itself. The new viruses then break out of the cell and infect other cells. HIV stores its genetic information on an RNA molecule rather than a DNA chromosome. This is a distinguishing characteristic of retroviruses , which are viruses that must first convert their RNA genomes into DNA before they can reproduce.

Each HIV virion (viral particle) is a small sphere composed of several layers. The external layer is a membrane coat, or envelope, obtained from the host cell in which the particle was made. Underneath this membrane lies a shell made from proteins, called a nucleocapsid. Inside the protein shell are two copies of the virion's RNA genome and three kinds of proteins, which are used by the virion to establish itself once inside the cell that it infects.

Two proteins, called gp120 and gp41, enable the virion to recognize the type of cell to enter. These proteins project from the HIV membrane coat. Gp120 binds to two specific proteins found on the target cell's surface (these target-cell proteins are called receptors). The first receptor, CD4, is found on immune system cells known as CD4 T cells, and also sometimes on two cell types known as macrophages and dendritic cells. The immune system uses CD4 T cells in the initial step in making antibodies against infectious agents. After binding to CD4, the HIV protein called gp120 binds with a second cell membrane protein, commonly referred to as the co-receptor. The co-receptor can be one of many different proteins, depending on the cell type. The two most common are CXCR4, which is normally found on CD4 T cells, and CCR5, a receptor found on CD4 T cells as well as on certain macrophages and dendritic cells. In the absence of HIV, CXCR4 and CCR5 allow these immune system cells to respond to chemical signals, but when HIV infects the cells, the HIV commandeers their usage. In some cases, individuals have a mutation in their co-receptor that prevents HIV from entering their cells.

Once gp120 has bound to both the CD4 receptor and co-receptor, the gp41 protein fuses HIV's membrane envelope with the cellular membrane, injecting the virus into the target cell. Once in the cytoplasm, the viral protein shell opens up and releases the viral proteins—a reverse transcriptase, a viral integrase, and a protease—along with the viral RNA strands. The reverse transcriptase copies the RNA strands into DNA. The viral integrase then helps insert the DNA copies into the cell's chromosome. At this point, the virus is called a provirus, and the life cycle halts. The provirus may remain dormant in the cell's chromosome for months or years, waiting for the T cell to become activated by the immune system.

HIV Life Cycle: Reproduction

When the immune system recruits T cells to fight an infection, the T cells start producing many proteins. Along with the normal cellular protein products, a T cell carrying an HIV provirus also produces HIV proteins. The first HIV proteins made are called Tat and Rev. Tat encourages the cellular machinery to copy HIV's proviral DNA into RNA molecules. These RNA molecules are then processed in the nucleus to become templates for several of the HIV proteins, some of whose functions are not well understood.

Rev, on the other hand, ushers the HIV's RNA molecules from the nucleus, where they are being reproduced, into the host cell's cytoplasm . Early in HIV reproduction, with only a few RNA molecules from which to make protein, a small quantity of Rev is made. Therefore, most of the RNA molecules remain in the nucleus long enough to get processed. As time passes, however, and Tat continues to instigate RNA production, more Rev is made. A higher amount of Rev protein increases the speed with which RNA molecules are ejected from the nucleus. These RNA molecules, which have undergone little or no processing, become templates to make different HIV proteins. The newer proteins are made in long chains that require trimming before they become functional. One of the proteins in the chain is the protease, the protein that trims. Other proteins include those that make up the protein shell, the reverse transcriptase, and integrase.

After the newly created proteins are processed to the right size, they form new virions by first assembling into a shell, then drawing in two unprocessed RNA molecules and filling up the remaining space with integrase, protease, and replicase. The new virions bud from the host-cell membrane, appropriating some of that membrane to form an outer coat in the process. The mature virus particles are now ready to infect other cells.

HIV's Immune-System Impairment Mechanism

One of the most disastrous effects of HIV infection is the loss of the immune system's CD4 T cells. These cells are responsible for recognizing foreign invaders to a person's body and initiating antibody production to ward off the infection. Without them, people are susceptible to a variety of diseases. HIV destroys the T cells slowly, sometimes taking a decade to destroy a person's immunity. However, in all the time before an HIV-infected individual shows any symptoms, the virus has been reproducing rapidly. The lymph tissue, the resting place for CD4 T cells, macrophages, and dendritic cells, becomes increasingly full of HIV, and viral particles are also released into the bloodstream.

HIV's main target is the population of CD4 T cells within a host's body. HIV kills them in one of three ways. It kills them directly by reproducing within them, then breaking them upon exit; it kills them indirectly by causing the cells to "commit suicide" by inducing apoptosis ; or it kills them indirectly by triggering other immune cells to recognize the infected T cell and kill it as part of the immune system's normal function.

As infected T cells die, the immune system generates more to take their place. As new T cells become infected, they are either actively killed or induced to commit suicide. Meanwhile, the HIV virus is not completely hidden from the immune system. As with any infectious agent, HIV presents its proteins to the immune system, which develops antibodies against it. This antibody production, however, is hampered by the fact that HIV mutates rapidly, changing the proteins it displays to the immune system. With each new protein, the immune system must generate new antibodies to fight the infection. Thus, an HIV infection is a dramatic balance between a replicating, ever changing virus and the replenishing stores of T cells that are fighting it. Unfortunately, the immune system, without therapeutic intervention, eventually loses the battle.

Once the CD4 T cells are depleted, the immune system can no longer ward off the daily bombardment of pathogens that all human organisms experience. Common infectious agents thus overwhelm the system, and HIV patients become susceptible to a variety of "opportunistic" diseases that take advantage of the body's reduced ability to fight them off. AIDS doctors report at least twenty-six different opportunistic diseases specific to HIV infection. These include unusual fungal infections such as thrush. The chickenpox virus may come out of dormancy, manifesting itself as the painful disease known as shingles. An obscure form of pneumonia, called pneumocystis pneumonia, is also common in AIDS patients. In addition, patients can acquire cancers such as B-cell lymphoma, which is a cancer of the immune system. Doctors generally consider patients with fewer than 200 CD4 T cells per cubic milliliter of blood as having AIDS. (In contrast, a healthy person counts more than 1,000.)

Anti-HIV Drug Therapy

Drugs that interfere with viral replication can slow down HIV disease. Early trials relied on the administration of one drug at a time. While patients' health improved and their T cell count rose, in time HIV mutated enough to render the drugs ineffective. Since 1995, however, doctors have found that rotating patients through three different drugs in very high doses significantly improves the health of AIDS patients. Known as "highly active antiretroviral therapy" (HAART), this therapeutic approach also reduces the amount of HIV circulating in the bloodstream to nearly undetectable levels. People infected with HIV who are treated by HAART are now living longer, healthier lives than ever before.

Targeting Life-Cycle Points

Drugs meant to knock out HIV target the activities of two HIV proteins, the reverse transcriptase and the protease. HAART requires drugs of both types. Drugs called protease inhibitors prevent the viral protease from trimming down the large proteins made late during infection. Without those proteins, the viral shell cannot be assembled. In addition, the proteins that reproduce HIV's genetic information, the reverse transcriptase and the integrase, are not functional.

Drugs that inhibit the reverse transcriptase prevent it from copying the RNA into DNA. These drugs work early in the life cycle of HIV. Reverse transcriptase inhibitors include azidothymidine (AZT), whose structure resembles the DNA nucleotide thymine. When reverse transcriptase builds DNA with AZT instead of thymine, the AZT caps the growing DNA molecule and halts DNA production, due to AZT's slight difference in structure from the thymine that DNA production requires.

see also Immune System Genetics; Retrovirus; Reverse Transcriptase.

Mary Beckman

Bibliography

Janeway, Charles A., et al. "Failures of Host Defense Mechanisms." In Immunobiology: The Immune System in Health and Disease, 4th ed. New York: Current Biology Publications, 1999.

———. HIV Infection and AIDS: An Overview. Washington DC: National Institute of Allergy and Infectious Diseases and U.S. Department of Health and Human Services, 2001.

Shilts, Randy. And the Band Played On: Politics, People, and the AIDS Epidemic. New York: St. Martin's Press, 2000. Stine, Gerald. Acquired Immune Deficiency Syndrome: Biological, Medical, Social and Legal Issues, 3rd ed. New York: Prentice-Hall, 1997.

HIV

Introduction

History and Scientific Foundations

Impact and Issues

BIBLIOGRAPHY

Introduction

The Human Immunodeficiency Virus (HIV) is the microorganism responsible for acquired immunodeficiency syndrome, or AIDS. HIV attacks the immune system, and eventually leaves the body vulnerable to potentially fatal opportunistic infections. An estimated 36 million people worldwide are infected with HIV.

History and Scientific Foundations

HIV is a type of “retrovirus” with a genetic code that is comprised of RNA rather than DNA. As it has no DNA, which is necessary to create RNA viral genome (genetic material) copies, it uses the DNA of infected host cells to create a new RNA genome for replicates (copies) of the virus. A retrovirus replicates by using a DNA intermediary, i.e., an infected cell's DNA. Retroviruses rely on the enzyme reverse transcriptase in order to perform the reverse transcription of its genetic code from its RNA into DNA, which can then be inserted into the host cell's genome using another enzyme. The virus then replicates as part of the cell's DNA. One of the major classes of HIV drugs targets reverse transcriptase, inhibiting the virus’ ability to create the DNA segment for insertion into the infected cell's DNA.

One of the most important features of HIV replication is its ability to generate large numbers of new genetic combinations through a process known as recombination. This, together with a high rate of genetic mutations of individual genes, enables HIV to rapidly create new drug-resistant strains. After HIV was identified as the cause of AIDS, researchers suspected that genetic recombination could also play a key role in the evolution of the virus. Very recently, studies of HIV infections worldwide have produced an estimate for the occurrence of HIV genetic recombination and have revealed that recombination frequencies appear to be much higher than expected. Recombination is currently regarded as a central aspect of the HIV infectious cycle.

HIV has a globular structure with a spiked envelope. The spikes on HIV virus carry the mystery of how the virus is attracted to CD4+ cells (a type of white blood cell) that play an important role in the immune system. The spikes on the HIV virus control the process by which the virus fuses with the targeted CD4+ cells. Despite intensive efforts by scientists, the spikes have been slow to reveal their structural and functional secrets. Recent advances are providing the first glimpses of the overall three-dimensional structure of the spiked envelope. Increasing knowledge of the viral envelope's component atomic structures offers new insights into the structural elements within the spike and could lead to entirely new avenues for the treatment of AIDS. The new treatments would target the ability of HIV to fuse with target cells, while current therapies interrupt viral replication.

The immune system has a so-called innate component (innate immunity) comprised of white blood cells called phagocytes, which migrate to affected areas and engulf disease-causing organisms (pathogens). Special cells of innate immunity called dendritic cells are particularly important for regulating immune response. When dendritic cells encounter foreign material, they have unique receptors that allow them to distinguish harmless and pathogenic (disease-causing) organisms. These cells carry fragments of pathogen to the lymph nodes, where they could stimulate a response by the adaptive immune system (called adaptive immunity), depending on the ability of the foreign material to cause disease.

If dendritic cells decide that the material is pathogenic (part of a virus or bacteria), they activate CD4+ helper T cells. (CD4+ refers to a surface protein on this type of T cell.) Helper T cells can then stimulate another group of white blood cells called B cells to produce antibodies that bind to the specific antigen and immobilize it, preventing it from causing infection. Antibodies are specific for only one antigen. Once activated, memory cells are produced that insure faster and stronger immune response when the body is re-exposed to the same pathogen.

Pathogens that escape antibody detection can enter and infect body tissue cells. The cell membrane of infected cells changes in a way that is recognized by T cells. Cytotoxic T cells kill infected cells, preventing them from producing more pathogen. Cytotoxic T cells must interact with Helper T cells to regulate the destruction of infected cells, in order to destroy cells that are infected by the specific microbe that has been presented to the helper cells by the dendritic cells.

HIV specifically attacks Helper T cells. Without an adequate number of Helper T cells, the immune system cannot signal B cells to produce antibodies to kill infected cells. When HIV has critically depleted the Helper T cell population, the body can no longer launch an adaptive immune response and becomes susceptible to many opportunistic infections, thus resulting in the immunodeficiency that characterizes AIDS. Research shows that the CD4+ membrane proteins are targets for HIV infection. Thus, memory helper T cells are quickly infected and destroyed in the mucus membranes of tissues. Only recently, researchers have recognized that the memory cell destruction occurs in the first several days after HIV infection, suggesting that therapies should begin as soon as the infection is detected.

Mysteries remain about how HIV causes disease, particularly the reason why there is uncontrolled viral replication in the majority of infected patients. In the past several years, investigation into HIV disease has focused on T regulatory (Treg) cells, a subset of CD4+ T-cells whose main function is to maintain a certain amount of tolerance in order to avoid autoimmunity (in which the immune system attacks the body's own tissues). Preliminary data point to two main roles for Treg cells in HIV: a detrimental effect in which HIV-specific immune responses are muted and a beneficial effect that limits immune activation (thus limiting the helper T-cell targets of HIV). There is currently a lack of standardized assays to measure levels and function of Treg cells, which continues to hamper research into this promising area. Thus, it is possible that HIV takes advantage of a feature of the immune system that naturally limits immune response.

WORDS TO KNOW

AUTOIMMUNITY: Autoimmune diseases are conditions in which the immune system attacks the body's own cells, causing tissue destruction. Autoimmune diseases are classified as either general, in which the autoimmune reaction takes place simultaneously in a number of tissues, or organ specific, in which the autoimmune reaction targets a single organ. Autoimmunity is accepted as the cause of a wide range of disorders, and is suspected to be responsible for many more. Among the most common diseases attributed to autoimmune disorders are rheumatoid arthritis, systemic lupus erythematosis (lupus), multiple sclerosis, myasthenia gravis, pernicious anemia, and scleroderma.

CD4+ T CELLS: CD4 cells are a type of T cell found in the immune system, which are characterized by the presence of a CD4 antigen protein on their surface. These are the cells most often destroyed as a result of HIV infection.

CYTOTOXIC: A cytotoxic agent is one that kills cells. Cytotoxic drugs kill cancer cells but may also have application in killing bacteria

OPPORTUNISTIC INFECTION: An opportunistic infection is so named because it occurs in people whose immune systems are diminished or are not functioning normally; such infections are opportunistic insofar as the infectious agents take advantage of their hosts’ compromised immune systems and invade to cause disease.

PATHOGEN: A disease causing agent, such as a bacteria, virus, fungus, etc.

RECOMBINATION: Recombination is a process during which genetic material is shuffled during reproduction to form new combinations. This mixing is important from an evolutionary standpoint because it allows the expression of different traits between generations. The process involves a physical exchange of nucleotides between duplicate strands of deoxyribonucleic acid (DNA).

Impact and Issues

The level of specificity of the science required to provide breakthroughs in the battle against HIV is unprecedented. Most disease cures and treatments that have been discovered during the past 100 years have been based on only limited knowledge of a microbe's ability to causes disease. As with the fight against cancer, the effort to find a cure for AIDS is leading scientists into ever more minute aspects of the pathogen, all the way down to the atomic structure of viral envelope spikes and the molecular mechanisms of genetic replication.

HIV is an amazingly versatile and adaptive enemy, probably owing to millennia of evolution in non-human primates and now being offered a new and relatively open ecological niche within humanity. While HIV transmission is preventable, a variety of social and behavioral factors have led to what will ultimately become the worst epidemic in terms of lives lost in the history of the human species. Also, as with the struggle against cancer, contending with the perplexing mysteries of HIV will leave a mark not only on the history and future development of medicine, but on human behavior and social evolution for the foreseeable future.

See AlsoAIDS (Acquired Immunodeficiency Syndrome); AIDS: Origin of the Modern Pandemic; Viral Disease.

BIBLIOGRAPHY

Books

Palladino, Michael A., and David Wesner. HIV and AIDS (Special Topics in Biology Series). San Francisco: Benjamin Cummings, 2005.

Periodicals

Sempere J.M., V. Soriano, and J.M. Benito. “T Regulatory Cells and HIV Infection.” AIDS Rev. (January–March 2007): 9 (1): 54–60.

Web Sites

University of Arizona: The Biology Project. “Immunology and HIV. Immune System's Response to HIV.” <http://www.biology.arizona.edu/immunology/tutorials/AIDS> (accessed June 8, 2007).

Kenneth T. LaPensee