Symptoms of Lymphadenopathy Syndrome (LAS)

• Unexplained fever
• Difficulty in swallowing
• Swollen glands
• Fatigue/Lethargy
• Night sweats and chills
• Apathy
• Gradual loss of weight
• Diarrhea
• Sore throat
• Impotence

Lymphadenopathy Syndrome (LAS)

Lymphadenopathy Syndrome (LAS) is a mild form of HIV infection, generally characterized by some of the symptoms in Figure 4.

Lymphadenopathy means "disease of the lymphatic system." The lymphatic system is the human body's second fluid system which contains a clear fluid called lymph (see Figure 3). The lymphatic system aids the blood system by draining fluid out of the body' s tissues. The lymphatic system is not a closed loop like the bloodstream, meaning it does not flow in a circle, and it has no pump like the heart. Nevertheless, lymph flows from smaller vessels into larger lymph ducts in the upper chest. In doing so, lymphatic fluid passes through a series of filtering stations called lymph nodes, or lymph glands. Lymph nodes filter bacteria (one-celled organisms), foreign substances, and dead white blood cells out of the fluid.

The lymphatic system is a vital part of the body's immune system. Lymph nodes store and mature lymphocytes and other white blood cells and also manufacture antibodies. T-cells and macrophages can migrate back and forth between the blood system and the lymphatic system, perhaps exposing newly generating cells to HIV during their formative stages.

Figure 3: The Lymphatic System

Healthy Carrier State

A carrier is someone who is infected with a disease and shows no clinical symptoms, but who is capable of infecting other people with the disease. ("Clinical" means "seen in the doctors office.")

HIV has been isolated (removed) and cultured ("grown" in a laboratory dish) from healthy people who show no clinical signs of HIV infection.

It is not yet clear when an HIV-infected person becomes infectious. At this time, the only safe practice is to assume that anyone carrying the virus is capable of transmitting it to others.

Types of HIV Infections (AIDS)

For the first few years of the AIDS epidemic, it appeared that some HIV-infected people sickened and died quickly while the others stayed healthy indefinitely or slowly progressed into sickness. Now it appears the greater majority of HIV-infected will gradually become very sick and eventually die. There are reports of long-term survivors of HIV infection; but, they seem to be the exception rather than the rule.

The average (the mean) incubation time for HIV infection is 10 years. Incubation time means the time from initial infection until the development of "full-blown AIDS," discussed below. The average is a bell curve, with 10 years at the center. Some individuals develop illness sooner than 10 years and some later than 10 years.

Most symptoms and diseases common to HIV infection are listed in Figures 4, 5 and 6. The presence of these symptoms and diseases varies from one patient to another. These diseases may occur in sequence or simultaneously.

Obviously, many of these symptoms can be caused by a number of common illnesses. These diseases are listed here for the sake of education, not for the purpose of self-diagnosis. In case of any persistent illness, consult your health care provider.

The popular classification system of HIV infections, used here, is a collection of haphazard definitions that evolved as the AIDS epidemic unfolded. These labels are ones of convenience, not ones of scientific or medical accuracy. Medical authorities use different, more complex, classification systems.

Basically, four loosely defined different stages of HIV infection exist: I ) the healthy carrier state, 2) the lymphadenopathy syndrome (LAS), 3) AIDS-related complex (ARC), and 4) AIDS or "frank AIDS," or "full-blown AIDS." These forms or the symptoms of each may overlap the other

Down the Road: New Drugs in the Pipeline

The Pharmaceutical Research and Manufacturers Association of America maintains a database of new drugs in development to treat HIV infection. They include new protease inhibitors and more potent, less toxic RT inhibitors, as well as other drugs that interfere with entirely different steps in the virus' lifecycle. These new categories of drugs include

• Entry inhibitors that interfere with HIV's ability to enter cells
• Integrase inhibitors that interfere with HIV's ability to insert its genes into a cell's normal DNA
• Assembly and budding inhibitors that interfere with the final stage of the HIV life cycle, when new virus particles are released into the bloodstream
• Cellular metabolism modulators that interfere with the cellular processes needed for HIV replication
• Gene therapy that uses modified genes inserted directly into cells to suppress HIV replication. These cells are designed to produce T cells that are genetically resistant to HIV infection.

In addition, scientists are exploring whether immune modulators help boost the immune response to the virus and may make existing anti-HIV drugs more effective. Therapeutic vaccines also are being evaluated for this purpose and could help reduce the number of anti-HIV drugs needed or the duration of treatment.

NIAID Research on the Complications of Antiretroviral Drugs

NIAID supports studies aimed at understanding the side effects of antiretroviral drugs as well as strategies to reduce exposure to potentially toxic drug regimens, such as

• Structured treatment interruption (STI) protocols
• Use of immune-based therapies with HAART
• Studies to compare different drug dosing schedules or combinations
• Studies to compare early versus delayed treatment

NIAID also supports projects evaluating regimens containing agents associated with toxicities. For example, NIAID-funded researchers are conducting studies to evaluate treatments for several drug-associated metabolic complications, including fat redistribution, lipid and glucose abnormalities, and bone loss. In addition, researchers are studying the long-term metabolic effects of various antiretroviral regimens in pregnant women and their infants and in HIV-infected children and adolescents.

Development of New Safe and Effective Antiretroviral Drugs

NIAID supports the development and testing of new therapeutic agents, classes, and combinations of antiretroviral drugs that can continuously suppress the virus with few side effects. Through human clinical trials, NIAID-supported studies provide accurate and extensive information about the safety and efficacy of drug candidates and combinations, and identify potential uncommon but important toxicities of newly approved agents. Studies are also under way to assess rare toxicities of older approved agents, especially as a result of long-term use.

Through the Multicenter AIDS Cohort Study and Women's Interagency HIV Study, NIAID supports long-term studies of HIV infection and its treatment in both men and women. Since their inception, these cohort studies have enrolled and collected data from more than 10,000 people. In addition, NIAID supports treatment studies conducted through three HIV/AIDS clinical trials networks: the AIDS Clinical Trials Group, the International Maternal Pediatric Adolescent AIDS Clinical Trials Group, and the International Network for Strategic Initiatives in Global HIV Trials.