Self & Other · When the System Is Quiet
The Quieter Conditions
The bulletin was the first official public notice of what would become the AIDS epidemic. Over the next two years, similar reports accumulated. By 1983, French and American researchers had identified the cause: a previously unknown retrovirus, eventually named the human immunodeficiency virus, or HIV. By the late 1980s, hundreds of thousands of people had died, and there was no effective treatment. The disease had what looked, at the time, like a one-hundred-percent fatality rate.
HIV does something that most viruses do not. It specifically infects, and over time destroys, the helper T cells we met in Chapter 3 — the conductors of the adaptive immune response, the cells without which B cells cannot mount strong antibody responses, killer T cells cannot be properly mobilized, and the entire orchestra of immunity falls apart. The virus does this slowly. After initial infection, an untreated person can feel relatively well for years — a decade, sometimes longer — while their helper T cell count slowly declines. When the count drops below a threshold, the system collapses. The patient becomes vulnerable to infections that any healthy person could brush off. They die, in most cases, of one or another of those opportunistic infections, not of HIV itself. The virus simply removes the conductors. The orchestra, leaderless, eventually falls silent.
Then, in 1996, the picture changed. A new class of drugs, used in combination with older ones, finally suppressed HIV replication well enough that the helper T cells could begin to recover. The treatment was called highly active antiretroviral therapy, or HAART. Within months, AIDS wards in major hospitals began to empty. Patients who had been preparing to die came home. The change was so dramatic that doctors who lived through it still describe it in tones usually reserved for religious experiences.
The drugs have continued to improve. As of the mid-2020s, an HIV-positive person who has access to modern antiretroviral therapy and takes it consistently has a life expectancy approximately equal to that of an HIV-negative person of similar background. The virus is suppressed below the level of detection. The immune system functions. There are even forms of treatment, taken before exposure, that can almost completely prevent infection in the first place — a class of preventive medications collectively called PrEP, which has dramatically reduced new infections in populations that have access to it. People living with well-treated HIV cannot transmit the virus to sexual partners; this fact, captured in public health campaigns by the equation Undetectable = Untransmittable, has been one of the more important shifts in how the disease is talked about.
This is, by any measure, one of the great medical accomplishments of the late twentieth century. It is also incomplete. There is, as yet, no cure — the virus persists, dormant, in cellular reservoirs, and treatment has to continue indefinitely. The drugs are expensive in many of the places where they are most needed, and the global picture remains uneven. About forty million people are living with HIV worldwide, and a significant fraction of them do not have reliable access to the medications that would, in a wealthy country, be entirely routine. The science has moved further than the equity has. The remaining work is largely about access.
The Quieter Conditions
SCID is rare. HIV, while still a global disease, is well understood. There is a much larger and stranger category of immunodeficiency that does not get either kind of attention, and that, statistically, you are far more likely to encounter in your life. These are the primary immunodeficiencies that show up not at birth but in adulthood, that look not like obvious disease but like “I just always seem to be sick.”
The most common is common variable immunodeficiency, or CVID. People with CVID make B cells, but the B cells fail to mature properly into the antibody-producing plasma cells we met in Chapter 3. The result is a person whose body, in many other ways, looks normal, but whose antibody levels are persistently low. They get the same infections everyone else gets. They just get them more often, and worse, and they take longer to clear them. They develop chronic sinus infections that don’t fully resolve. They get pneumonia from things their friends don’t notice. They have unexplained fatigue. They are sometimes told, for years, that nothing is wrong with them — because their basic blood counts look normal, and because no one thought to measure their antibody levels.
CVID affects roughly one in twenty-five thousand people, which makes it more common than most genetic diseases people have heard of. Diagnosis often takes years. The treatment, when it is identified, is straightforward in concept: regular infusions of immunoglobulin — antibodies pooled from the blood donations of thousands of healthy donors — given either intravenously every few weeks or under the skin more frequently. The infused antibodies do, temporarily, what the patient’s own B cells cannot. The infections that had been chronic become rare. The person, often for the first time in years, feels well.
There are dozens of other primary immunodeficiencies, each with its own pattern. Selective IgA deficiency, in which the antibody class that protects mucosal surfaces is missing, is surprisingly common — perhaps one in five hundred people — though many of those people never know they have it because they remain mostly healthy. Bruton’s agammaglobulinemia, an X-linked disease, eliminates B cells entirely. Hyper-IgE syndrome causes recurrent skin and lung infections combined with eczema. DiGeorge syndrome involves the absence or near-absence of a thymus, which means — as Jacques Miller’s mice in Chapter 7 demonstrated — a profoundly impaired T cell system. Each of these has its own genetics, its own age of onset, its own pattern of vulnerability. Each is, in principle, identifiable through testing. Many of them have specific treatments.