Aids Research

AIDS

I INTRODUCTION

Acquired Immune Deficiency Syndrome (AIDS), specific group of diseases or conditions that result from suppression of the immune system, related to infection with the human immunodeficiency virus (HIV). A person infected with HIV gradually loses immune function along with certain immune cells called CD4 T-lymphocytes or CD4 T-cells, causing the infected person to become vulnerable to pneumonia, fungus infections, and other common ailments. With the loss of immune function, a clinical syndrome (a group of various illnesses that together characterize a disease) develops over time and eventually results in death due to opportunistic infections (infections by organisms that do not normally cause disease except in people whose immune systems have been greatly weakened) or cancers.

In the early 1980s deaths by opportunistic infections, previously observed mainly in organ transplant recipients receiving therapy to suppress their immune responses, were recognized in otherwise healthy homosexual men. In 1983 French cancer specialist Luc Montagnier and scientists at the Pasteur Institute in Paris isolated what appeared to be a new human retrovirus--a special type of virus that reproduces differently from other viruses--from the lymph node of a man at risk for AIDS (see Lymphatic System). Nearly simultaneously, scientists working in the laboratory of American research scientist Robert Gallo at the National Cancer Institute in Bethesda, Maryland, and a group headed by American virologist Jay Levy at the University of California at San Francisco isolated a retrovirus from people with AIDS and from individuals having contact with people with AIDS. All three groups of scientists isolated what is now known as human immunodeficiency virus (HIV), the virus that causes AIDS.

Infection with HIV does not necessarily mean that a person has AIDS, although people who are HIV-positive are often mistakenly said to have AIDS. In fact, a person can remain HIV-positive for more than ten years without developing any of the clinical illnesses that define and constitute a diagnosis of AIDS. In 1997 an estimated 30.6 million people worldwide were living with HIV or AIDS--29.5 million adults and 1.1 million children. The World Health Organization (WHO) estimates that between 1981, when the first AIDS cases were reported, and the end of 1997, more than 12.9 million adults and children had developed AIDS. In this same period there were 11.7 million deaths worldwide from AIDS or HIV. About 430,000 of these deaths occurred in the United States.

II CLINICAL PROGRESSION OF AIDS

The progression from the point of HIV infection to the clinical diseases that define AIDS may take six to ten years or more. This progression can be monitored using surrogate markers (laboratory data that correspond to the various stages of disease progression) or clinical endpoints (illnesses associated with more advanced disease). Surrogate markers for the various stages of HIV infection include the declining number of CD4 T-cells, the major type of white blood cell lost because of HIV infection. In general, the lower the infected person's CD4 T-cell count, the weaker the person's immune system and the more advanced the disease state. In 1996 it became evident that the actual amount of HIV in a person's blood--the so-called viral burden--could be used to predict the progression to AIDS, regardless of a person's CD4 T-cell count. With advancing technology, viral burden determinations are quickly becoming a standard means of patient testing.

An infected person's immune response to the virus--that is, the person's ability to produce antibodies against HIV--can also be used to determine the progression of AIDS; however, this surrogate marker is less precise during more advanced stages of AIDS because of the overall loss of immune function.

Within one to three weeks after infection with HIV, most people experience nonspecific flulike symptoms such as fever, headache, skin rash, tender lymph nodes, and a vague feeling of discomfort. These symptoms last about one to two weeks. During this phase, known as the acute retroviral syndrome phase, HIV reproduces to very high concentrations in the blood, mutates (changes its genetic nature) frequently, circulates through the blood, and establishes infections throughout the body, especially in the lymphoid organs. The infected person's CD4 T-cell count falls briefly but then returns to near normal levels as the person's immune system responds to the infection. Individuals are thought to be highly infectious during this phase.

Following the acute retroviral syndrome phase, infected individuals enter a prolonged asymptomatic phase--a symptom-free phase that can last ten years or more. Persons with HIV remain in good health during this period, with levels of CD4 T-cells ranging from low to normal (500 to 750 cells per cubic mm of blood). Nevertheless, HIV continues to replicate during the asymptomatic phase, causing progressive destruction of the immune system.

Eventually, the immune system weakens to the point that the person enters the early symptomatic phase. This phase can last from a few months to several years and is characterized by rapidly falling levels of CD4 T-cells (500 to 200 cells per cubic mm of blood) and opportunistic infections that are not life threatening.

Following the early symptomatic phase, the infected person experiences the extensive immune destruction and serious illness that characterize the late symptomatic phase. This phase can also last from a few months to years, and the affected individual may have CD4 T-cell levels below 200 per cubic mm of blood along with certain opportunistic infections that define AIDS. A wasting syndrome of progressive weight loss and debilitating fatigue occurs in a large proportion of people in this stage. The immune system is in a state of severe failure. The person eventually enters the advanced AIDS phase, in which CD4 T-cell numbers are below 50 per cubic mm of blood. Death due to severe life-threatening opportunistic infections and cancers usually occurs within one to two years.

III OPPORTUNISTIC ILLNESSES

Death from AIDS is generally due not to HIV infection itself, but to opportunistic infections that occur when the immune system can no longer protect the body against agents normally found in the environment. The appearance of any one of more than 25 different opportunistic infections, called AIDS-defining illnesses, along with a CD4 T-cell count of less than 200 cells per cubic millimeter of blood provides the clinical diagnosis of AIDS in HIV-infected individuals.

The most common opportunistic infection seen in