Chapter 2
Anatomy of an Infection

In the years following the discovery of HIV, much has been learned about the disease called AIDS. Scientists have worked to sort out misconceptions and get the truth to the public. In the two decades since the initial diagnoses of AIDS, it has been well established how HIV is transmitted and what behaviors are considered high risk. Furthermore, doctors have become more aware of the specific physiological changes that occur during each stage of the disease, resulting in treatment plans that can target the virus at its most vulnerable points, thereby improving the quality of life of AIDS patients.

Panic

The HIV blood test had great implications for public health. The infection rate from blood transfusions dropped to nearly zero when the HIV test was used for screening purposes. Furthermore, the spread of the disease could be better controlled when doctors could identify and then counsel infected individuals on how to keep from spreading the disease. People who were informed that they carried the virus could also begin treatment before symptoms arose, resulting in increased longevity.

The public health benefits were almost forgotten, though, when HIV testing proved how extensively the virus had spread through the population. The American public practically panicked. People were confused about ways that HIV could and could not be transmitted, and conflicting reports from doctors made many sectors of the public somewhat distrustful of the medical profession. While the CDC maintained that HIV could be transferred only through bodily fluids such as blood and semen, some doctors openly expressed the belief that the virus could be transmitted through contact as casual as "sharing a bologna sandwich,"¹² in the words of one observer. Another report stated that HIV could be excreted in tears. According to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, "Somehow that sprang a fear that it [HIV] must be all over the place."¹³

Parents like Darlynn Spizzeri, a New York City mother, kept their children out of school because "we are afraid our children will catch the disease even if those so-called, quote-unquote experts say it is impossible."¹⁴ There was talk about quarantining HIV-infected individuals, or at least making it illegal for them to engage in sexual activities.

Scientists, who understood that many of the public's fears were based in misconceptions, now struggled to find ways to prove that the fears were mostly unfounded. Work began to raise consciousness about HIV and AIDS and to define the course of the disease more clearly.

HIV Transmission

Some of the most important information to be gained after HIV was discovered was a better understanding of the ways in which the virus could be transmitted. Despite many conjectures and myths that sprang up when the public first learned about AIDS, the CDC identified specific high-risk behaviors for contracting HIV and ascertained that the disease could not be spread through casual contact.

Further research confirmed that the virus could be found in bodily fluids as diverse as saliva, tears, blood, breast milk, semen, urine, and vaginal secretions. Many believed that this pervasive presence of HIV would prevent doctors from achieving control over the epidemic. In reality, though, as stated by Stephen Schultz, the assistant commissioner of the New York City health department in 1985, "AIDS is not an easy disease to come by. It is hard to get [from casual contact]."¹⁵ This observation has held true through all the subsequent investigations.

There are several reasons that HIV is considered fairly difficult to contract outside the defined high-risk behaviors. The probability that a person will be infected with HIV upon exposure to the virus depends on what kind of bodily fluid is being exchanged, the concentration of virus in that fluid, how long the fluid has been out of an infected individual's body, and how the virus enters the body of the recipient. The high number of variables involved in a successful infection often puts the odds against getting HIV, especially when proper precautions are taken.

In an infected person, fluids such as blood, semen, vaginal secretions, and breast milk have relatively high concentrations of HIV; an exchange of these fluids carries with it a high risk of contracting HIV. However, fluids such as saliva, tears, and urine have low levels of HIV and pose a low risk of transmitting HIV. Saliva, in fact, is a particularly hostile environment for HIV: Because of the strong digestive

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enzymes present, saliva will kill up to half of the viruses exposed to it within thirty minutes. In fact, because of this harsh environment, HIV is unlikely to be spread through activities such as kissing, unless there are open sores in the mouths of the people involved.

Since casual contact, such as shaking hands, hugging, or using the same seats, elevators, or bathrooms as infected people, does not involve exposure to high-risk bodily fluids, the danger of becoming infected with HIV in this way is practically nil. According to Dr. Mirko Grmek, "There is absolutely no evidence that AIDS has ever been spread under normal living conditions—not in schools, not in crowded buses or trains, not in restaurants, not at the hairdressers', not in business meetings."¹⁶

Risky Behavior

As it turns out, the human skin is an excellent barrier against most microbes, including HIV. Because of this, simple contact with HIV-infected fluids will not result in infection. The fluid must enter the individual's body and get past the body's natural defenses for an infection to occur.

People who run the highest risks of contracting HIV are those who engage in unprotected sex with an infected person and intravenous drug users who share needles with HIV-positive individuals. Health care workers who come into contact with bodily fluids such as blood and semen also run a significant risk of contracting HIV, but this risk is usually reduced by routine precautions, such as the use of rubber gloves when handling biological specimens. Pregnant mothers who are HIV-positive and transmit the virus to their children do so either in the womb or during birth through blood contact.

Since blood used for transfusions in the United States is now routinely screened for HIV, this is no longer considered high risk, although it is still theoretically possible to become infected through transfusion. Blood transfusions do remain a risk for transmitting HIV in other parts of the world, however, especially in underdeveloped areas where the blood supply is not screened as thoroughly. For example, in 2001, it was reported that tens of thousands of villagers in China's Henan Province contracted HIV through infected blood.

Preliminary Signs

As HIV transmission became better understood, further spread of the disease could be prevented. People were informed about high-risk behaviors and what precautions, such as using condoms during sexual intercourse and not sharing needles for intravenous drug use, should be taken to reduce the risk of contracting HIV. These precautionary measures did not, however, offer any solace to those already infected. To help these people, better understanding of the infection process itself had to be gained.

What researchers have learned is that after HIV enters the body of a new host, the virus particles seek out helper T cells in the bloodstream. When an HIV particle encounters a T cell, the virus attaches to proteins on the surface of the cell and then fuses its viral membrane to the cell membrane. Upon fusion, HIV injects its genetic material into the cell and begins the process of replication.

Early studies of AIDS were aimed at understanding the way the disease progresses in infected individuals and drew attention to some of the preliminary signs of HIV infection. It was found, for example, that many of the people who had AIDS recalled noticing flu-like symptoms long before they experienced the opportunistic infections that are the hallmarks of AIDS. Patients suffer from symptoms like fever, fatigue, diarrhea, rash, swelling of the lymph nodes, mild muscle aches, and headaches. These symptoms often go unnoticed as they are relatively mild and are often assumed to be indicative of less serious infections such as mononucleosis. The initial infection is also associated with fluctuations in T cell levels, but those quickly return to normal.

Since the initial symptoms are fairly mild and the victim returns to feeling healthy, many people who subsequently test positive for HIV have a hard time accepting that they carry a life-threatening virus. Upon learning that he was HIV infected, Raul of East Los Angeles declared in 1996, "I've thought about it, but I just can't picture it happening to me. I think I'll probably die of something else."¹⁷

A Virus Factory

It is now well understood that the flu-like symptoms that are the hallmark of initial HIV infection are the results of the body's initial attempt to battle the virus. In this stage, referred to as the acute stage of infection, the virus rapidly infects specialized cells called helper T cells and multiplies quickly. Because HIV is able to integrate its own viral genetic material to that of the host cell, it can trick the host into producing viral proteins during the normal life cycle of the cell, turning the host into a living HIV factory. New HIV particles bud off the host cell and are released into the bloodstream.

Very high levels of HIV are present in the blood during acute infection. In fact, more than 10 billion new viral particles are produced each day of this phase. Because so much of the virus is produced, this is the most infectious stage of the disease; HIV-positive individuals are more likely to infect others during acute infection than they are later on.

The immune system fights the initial infection with killer T cells, whose numbers increase during this stage, and will eventually supplement the attack with antibodies produced by another type of immune cell, the B cell. This immune response aims to kill as many virus-infected cells as possible to contain the infection. In this case, these virus-infected cells are helper T cells, responsible for helping B cells produce antibodies. Unfortunately for the patient, the immune system is unable to clear HIV completely from the body.

The Virus Lies in Wait

At some point in its response to HIV infection, the body begins producing antibodies to the virus. Enough helper T cells survive the

initial onslaught of HIV to allow B cells to generate HIV-specific antibodies. This point is referred to as seroconversion, when a blood test can detect HIV-positive status.

Overall, the body is able to control HIV in the early stages of the disease. Since the body mounts a strong immune response, the vast majority of HIV particles are cleared from the body almost as soon as they are produced. Eventually, the number of viral particles in

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the blood declines, and new helper T cells are produced at a high enough rate to return their levels to normal. The patient enters a stage known as clinical latency, a time during which HIV does not cause harmful symptoms.

During clinical latency, reservoirs of HIV are found in lymphoid tissues, such as the lymph nodes. HIV also continues to hide in certain immune cells. Since the viral DNA is integrated into the DNA of these cells, permanent HIV reservoirs are created as long as those cells or their descendants live. This is extremely problematic for fighting the disease because, even though the viral particles in the bloodstream are destroyed by the immune system, the HIV that remains hidden is protected from the immune response. Drugs administered to HIV-positive patients cannot completely eliminate the virus in these reservoirs either. "We now know that these reservoirs are established very early in the course of infection,"¹⁸ says Fauci.

Although there are far fewer viral particles detected by blood tests during clinical latency than in the acute stage, HIV is still transmissible. In fact, each year of the dormant phase of HIV infection, which can last on average between two and fifteen years, more and more virus emerges from the concealed reservoirs. The numbers of HIV particles produced each day are astronomical. "We've learned that 10 billion to 1 trillion HIV viruses are produced in one day in the human body,"¹⁹ says Dr. David Ho. The viral load in the blood seems to remain constant because the body fights back daily, clearing the viral particles continuously. "It's like a person running on a treadmill,"²⁰ Ho explains. This constant level of viral concentration established during latency, which in the average patient ranges between ten thousand and one hundred thousand HIV particles per milliliter of blood, usually stays relatively constant.

This constant onslaught of virus, which must be continually cleared, gradually weakens the immune system. In other words, the treadmill effect slows, and the virus begins to win. As the immune system sustains damage, HIV-positive patients may experience mild, nonspecific symptoms, such as skin rashes, fatigue, slight weight loss, night sweats, or yeast infections in the mouth. These phenomena do not necessarily mean that AIDS is imminent, but in an immune-compromised HIV-positive individual, the risks of developing even more serious symptoms increase.

Onset of AIDS and Decline

No matter how strong an immune response the body mounts, most HIV-positive individuals can achieve only temporary control over the virus. The number of helper T cells that would normally aid in the production of antibodies to fight the infection gradually declines, weakening the immune response. This allows the virus to gain a stronger foothold in the body. The concentration of HIV in the blood increases, and subsequently more T cells are infected and killed. As the cycle continues, the infected individual suffers more infections and other health problems. Interestingly, there seems to be a correlation between the level of viral concentration during latency and the length of the dormant period: the higher the concentration of blood HIV in latency, the more rapidly the patient will progress to AIDS.

The point at which doctors say an HIV infection has turned into AIDS is defined by a patient meeting criteria set by the CDC. According to the CDC's current definition, a person is considered to have AIDS when he or she tests positive for HIV and has either a helper T cell count of less than two hundred cells per milliliter of blood (normal levels are between five hundred and eighteen hundred) or has at least one opportunistic infection. The most common opportunistic infections included in the CDC's definition of AIDS are some that had been diagnosed in the earliest AIDS patients: Pneumocystis carinii pneumonia (PCP); Kaposi's sarcoma (KS); cryptococcosis; yeast infections (Candidiasis) of the esophagus, trachea, bronchi, or lungs; cytomegalovirus disease (CMV); and toxoplasmosis of the brain.

Once AIDS develops, the patient can rarely survive more than two years without treatment from drugs designed to combat HIV. In the late stages of AIDS, the body is left without an immune system. Practically all the helper T cells are eliminated, rendering the immune system unable to produce antibodies against infections. The body can no longer mount an immune response, even to the mildest pathogens. Even when antibitotics and other drugs are administered, opportunistic infections run rampant. Eventually, the effects of the infections kill the patient.

Avenues for Treatment

With greater understanding of the way HIV infection affects the body and how it develops into AIDS, researchers have found potential avenues for treatment. For example, having identified HIV as a retrovirus, scientists have been able to use the particular characteristics of this type of virus against it. Although they have yet to find a drug that kills HIV, they have made strides in developing drugs that slow the virus's growth. With the advent and development of these and other drugs, doctors believe they are on the verge of converting AIDS from a terminal illness to a chronic, yet manageable, disease.