How We Die (30 page)
Authors: Sherwin B Nuland
It is no easy matter to explain or understand the mechanism by which the many opportunistic invaders lay waste the body of an adult or child with AIDS. Such a baffling array of problems is faced by the HIV-infected and their caregivers that one cannot but contemplate with a sense of awestruck gratitude that so much has already been accomplished. When a doctor of my generation makes hospital rounds with an AIDS team of physicians and nurses, all he can do is figuratively gasp at how much these skilled clinicians know and what a large proportion of it has been learned in so short a time. Every patient on the unit carries a multitude of infections and sometimes one or two cancers; each is receiving four to ten or even more medications, without any certainty of predictable response or toxicity—Ishmael Garcia was on fourteen. Daily, and sometimes more often, new decisions must be made about everyone being treated (my hospital’s relatively small AIDS area has forty beds, and they are always full).
As if the immensity of the clinical challenges were not enough, distraught families wait nearby for answers, and for consolation as well; there are reports for the staff to fill out, charts to review, tests to order, students to teach, conferences to attend, and an ever-burgeoning new literature to read and often to contribute to. And always, the most important charge is to care for those dreadfully stricken brothers and sisters of all of us, the sickest of whom are wasted, feverish, swollen, and anemic, their eyes seeking some reassurance and the unspoken promise of relief from their torment, which too often will come only with death. No matter the perseverance and moral strength so many patients muster in the face of lethal certainty, the pitiless process by which they die is dispiriting anew with every reenactment.
IX
The Life of a Virus and the Death of a Man
T
HE DISCOVERIES THAT
were being so rapidly made about the life cycle of the virus provided the background against which to seek points where it might be vulnerable to attack. Viewed simply, a virus is nothing more than a tiny particle of genetic material enclosed within the envelope of protein and fatty materials. Viruses are the smallest known living things, and they carry very little genetic information. Because they can’t exist without the help of more complex structures, they must live within cells. Since a virus cannot reproduce (in the case of a virus, scientists prefer the term
replicate
) on its own, like a bacterium, for example, it must get itself inside a cell and take control of the cell’s genetic machinery by becoming integrated into it. HIV accomplishes this by a method that is the reverse of the ordinary process by which genetic information is transmitted; for that reason, it is called a retrovirus.
HE DISCOVERIES THAT
were being so rapidly made about the life cycle of the virus provided the background against which to seek points where it might be vulnerable to attack. Viewed simply, a virus is nothing more than a tiny particle of genetic material enclosed within the envelope of protein and fatty materials. Viruses are the smallest known living things, and they carry very little genetic information. Because they can’t exist without the help of more complex structures, they must live within cells. Since a virus cannot reproduce (in the case of a virus, scientists prefer the term
replicate
) on its own, like a bacterium, for example, it must get itself inside a cell and take control of the cell’s genetic machinery by becoming integrated into it. HIV accomplishes this by a method that is the reverse of the ordinary process by which genetic information is transmitted; for that reason, it is called a retrovirus.
The genetic material of cells is composed of the strands of molecules called deoxyribonucleic acid (DNA); DNA is the repository of genetic information. Under ordinary conditions of reproduction, DNA is copied, or “transcribed,” into other molecular strands called ribonucleic acid (RNA), which functions as a template to direct the production of the new cell’s proteins. In a retrovirus, however, the genetic material is RNA. The retrovirus also carries an enzyme called reverse transcriptase, which, once the virus enters the host cell, transcribes the RNA into DNA, which is then translated in the usual proper sequence into proteins.
The series of events that takes place when a lymphocyte is infected by HIV is roughly as follows: The virus binds to structures called CD4 receptors on the membrane surrounding the cell; at those points, it sheds its envelope as it is taken into the cell, where its RNA is transcribed to DNA. The DNA then migrates into the lymphocyte’s nucleus and inserts itself into the cell’s own DNA. For the rest of that lymphocyte’s lifetime and the lifetime of its progeny, it remains infected with the virus.
From this point on, every time an infected cell divides, the viral DNA is duplicated along with the cell’s own genes and remains as a latent infection. For unknown reasons, at some point the viral DNA dictates the production of new viral RNA and viral proteins; in this way, new viruses are manufactured. They bud off from the lymphocyte’s cell membrane, are set free, and then go on to infect more cells. If the process is fast enough, it can kill the lymphocyte that harbors it, which is destroyed as the virus particles burst out. Yet another method of lymphocyte destruction makes use of the fact that certain structures on the surface of the newly budded virus can bind to still-uninfected T cells, with the result that large numbers of the cells fuse together into clumps called syncytia. Because syncytia can no longer function in immunity, the clumping proves to be a very effective way of inactivating many lymphocytes at once.
As noted earlier, the cell attacked by HIV is the T lymphocyte, a white blood cell that has a major role in the body’s immune response. Specifically, it is a subset of the T cells called CD4, or T4, lymphocytes (yet another name is the helper T cell) that is victimized. So dominant is the CD4 cell in the overall functioning of the immune system, it has been called its “quarterback.”
HIV can thus affect CD4 cells in various ways. It can replicate in them, can lie dormant for long periods of time, and can also kill or inactivate them. It is the enormous depletion of CD4 lymphocytes gradually occurring over time that is the major factor in preventing a patient’s immune system from mounting an effective defense against various forms of infections by bacteria, yeasts, fungi, and other microorganisms.
HIV attacks another type of white blood cell as well, called the monocyte, of which as many as 40 percent have the CD4 receptor in their membrane, and can thus take on the virus. Yet one more refuge is the macrophage (literally, the “big eater”), among whose functions is the ingestion and destruction of infectious cellular debris. Unlike the CD4 lymphocyte, neither the macrophage nor the monocyte is destroyed by HIV; they seem to be used as reservoirs and safe houses in which the microbe may lie dormant for long periods of time.
All of the foregoing is but a sketchy outline of the way in which the immune system is gradually laid waste by HIV. Although some have protested the use of military analogies to portray the pathophysiology of disease, AIDS lends itself particularly well to such descriptive comparisons. The process, in fact, is not unlike a gradual buildup of forces, during the later stages of which a prolonged artillery and air bombardment destroys a country’s defenses in preparation for a massive land invasion carried out by a large coalition of belligerents, allied together to accomplish total annihilation. The army of microbes that kills the victim of AIDS after HIV has knocked off his CD4 cells includes many different kinds of divisions, and every one of them has its own target and its own lethal mechanism of attack. The most conservative epidemiologists predict that by the year 2000, there will be 20 to 40 million sero-positive people on our planet who are under siege or already invaded. Forty to eighty thousand Americans are becoming newly infected each year, and the same number die.
As far as has yet been determined, there are only three ways in which infection can take place: via sexual contact, an exchange of blood (as with a contaminated needle, syringe, or blood products), or transmission from an infected mother to her child in the uterus, at the time of delivery, or even in the breast milk postnatally. HIV has been isolated in the laboratory from blood, semen, vaginal secretions, saliva, breast milk, tears, urine, and spinal fluid, but only blood, semen and breast milk have ever been found to transmit the disease. Since 1985, the banked blood supply has been so carefully screened that the possibility of contracting HIV from transfusion is remote. In the United States and most developed nations, the overwhelming majority of those infected by the sexual route are gay or bisexual men, but in Africa and Haiti, the great predominance is among heterosexuals. Although the number of heterosexually transmitted cases remains low in the West, it is gradually rising, as is the number of infected infants. Approximately one-third of the Americans who become infected each year are intravenous drug abusers, and at least an equal number are gay men. The remainder, most of whom are black and Hispanic women, acquire the disease heterosexually, and their seropositivity explains why two thousand babies are born infected each year.
AIDS is a disease of low contagion. HIV is a very fragile virus—it is not easy to become infected with it. Simple household bleach in a 1:10 dilution kills the virus efficiently, as do alcohol, hydrogen peroxide, and Lysol. Within twenty minutes of being poured on a tabletop and allowed to dry, virus-laden fluid is no longer infective. One need not fear any of the four bugbears (or bug-bearers) so often avoided by the germ-shy: insects, toilet seats, eating utensils, and kissing. Although there are certainly cases thought to have been transmitted by a single sexual encounter, seropositivity usually requires a very high dose of virus or repeated episodes of contact. In the United States, the risk of seropositivity via a chance heterosexual intimacy is real but very small. As reassuring as it may be to contemplate the difficulties that must be overcome by the virus in order to infect us, the sense of security disappears in the face of the grim fact that once infected, we are likely to die. That consideration alone justifies the precautions urged on us by public health authorities.
The virus often shows its hand very soon after entering a new host. Within a month or less, rapid replication causes its concentration in the blood to become extremely high, and it stays that way for about two to four weeks. Although many newly infected people remain without symptoms, others during this period develop low-grade fevers, swollen glands, muscle aches, a rash, and sometimes central nervous system symptoms such as headaches. Because these symptoms are not specific and may also be accompanied by a general sense of fatigue, they are often erroneously attributed to flu or mononucleosis. As this brief syndrome is ending, the first antibodies against HIV begin to appear in the blood; a blood test will detect them, and the patient is henceforth sero-positive. Although the short symptomatic period ends, the virus continues to replicate.
Very likely, the brief mononucleosislike syndrome is caused by the first response of the body’s immune system to the alarm set off by the massive number of new virus particles that have by then been produced. The body is initially successful, and the number of virus-particles in the blood drops dramatically to low levels. What seems to have happened at this point is a retreat by the remaining microbes into CD4 lymphocytes, lymph nodes, bone marrow, the central nervous system, and spleen, where they lie dormant for years or replicate so slowly that the total low concentration in the blood remains stable. Actually, only 2 to 4 percent of the body’s CD4 cells are in the blood. Most likely, those in the lymph nodes, spleen, and marrow are being gradually destroyed during the long dormant period, but the destruction is not reflected in the blood until the end of this time, when the CD4 counts, having remained constant till then, begin to drop dramatically, allowing the multiple secondary infections that characterize AIDS to ensue. At that point, the amount of virus in the blood rises again. The reason for the prolonged period of relative inactivity is unknown, but it does suggest that the body’s immune system may be playing some role in mitigating the infection, at least that part of it which is restricted to the blood itself. When the immune system has sufficiently deteriorated, the amount of virus in the lymphocytes and free in the blood increases markedly.
This sequence of events may explain why most HIV-positive people develop swollen lymph glands in the neck and armpits during the early two-to-four-week period of symptoms, which do not recede at the end of it. When that period is over, patients continue to feel well for an average of three to five years or even ten years, by the end of which time examination of the blood will usually reveal that the number of CD4 cells has declined considerably, from a normal count of 800 to 1,200 per cubic millimeter to below 400. This means that 80 to 90 percent of these lymphocytes have been destroyed. On an average of eighteen months later, standard skin tests for allergy begin to show that the immune system is becoming impaired. The CD4 count continues to drop, but patients at this stage of disease still may not have begun to show evidence of clinical illness. In the meantime, the level of virus in the blood is rising and the swollen lymph nodes are slowly being destroyed.
When the CD4 cell count falls below 300, the majority of patients will develop the fungal infections of the tongue or oral cavity called thrush, which presents itself as white patches in those areas. Other infections that may begin to appear when the count is below 200 are herpes around the mouth, anus, and genitals, as well as a severe vaginal infection with the same fungus that caused the thrush. A characteristic finding is a condition called oral hairy leukoplakia (from the Greek
leukos
—meaning “white,” and
plakoeis
—meaning “flat”) a group of fuzzy-looking vertical white patches standing upright like corrugations along the lateral margins of the tongue. These lesions are due to a virus-induced thickening of the surface layers.
leukos
—meaning “white,” and
plakoeis
—meaning “flat”) a group of fuzzy-looking vertical white patches standing upright like corrugations along the lateral margins of the tongue. These lesions are due to a virus-induced thickening of the surface layers.
Within a year or two of this time, many patients are beginning to develop opportunistic infections in areas beyond the skin and body openings. By then, the CD4 cell count has usually fallen well below 200 and is dropping rapidly. The entire syndrome of immune deficiency begins to make itself evident as diseases appear that are caused by microbes ordinarily living in perfectly healthy people whose normal physiological defenses prevent trouble. The stage has now been reached at which serious pathology can be caused by any organism that requires intact immunity to combat it. Although people with AIDS are highly susceptible to well-known diseases such as tuberculosis and bacterial pneumonia, they are also set upon by a group of otherwise-unusual sicknesses due to a variety of parasites, fungi, yeasts, viruses, and even bacteria that physicians rarely encountered before the advent of HIV. For some of these organisms, there was no effective treatment until the late 1980s, when the efforts of university laboratories and the pharmaceutical industry were finally rewarded with the development of a group of drugs that have shown varying degrees of clinical success.
Other books
The Compelled by L J Smith
Lessons From a Younger Lover by Zuri Day
The Lone Pilgrim by Laurie Colwin
First Murder by Limberg, Fred
Argh Fuck Kill: The Story of the DayGlo Abortions by Chris Walter
Sacred Sword (Ben Hope 7) by Scott Mariani
The Railway Station Man by Jennifer Johnston
Hush by Carey Baldwin
The Mystery of Olga Chekhova by Antony Beevor
They Say Love Is Blind by Pepper Pace