AIDS, Recent Advances in Research and Treatment (World of Microbiology and Immunology)
Acquired Immune Deficiency Syndrome (AIDS) has only been known since the early years of the 1980s. Since that time, the number of people infected with the causative virus of the syndrome and of those who die from the various consequences of the infection, has grown considerably.
In the 1980s and 1990s, researchers were able to establish that the principle target for the maladies associated with AIDS is the immune system. Since then, much research has been directed towards pinpointing the changes in the human immune system due to infection, seeking ways of reversing these changes, or supplementing the compromised immune system to hold the infection in check.
The particular immune system component that has been implicated in the progression of AIDS is a type of T cell called the CDC4 T cell. This cell, which is activated following recognition of the virus by the immune system, functions in the destruction of the cells that have been infected by the virus. Over time, however, the number of CDC4 cells declines. If the decline decreases the T cell count to below 200 per microliter of blood, the number of infective virus particles goes up steeply and the immune system breaks down. This loss of the ability to fight off foreign organisms leaves the patient open to life-threatening illnesses that normally would be routinely defeated by an unimpaired immune system.
Until 2001, the prevailing view was that the decline in the number of CDC4 cells was due to a blockage of new T cell production by the infecting virus. However, the conclusions from studies published in 2001 now indicate that the production of new T cells is not blocked, but rather that there is acceleration in the loss of existing T cells. Even though the result is the same, namely the increased loss of the specialized AIDS-fighting T cells, the nature of the decline is crucial to determine in order to devise the most effective treatment strategy. If the reasons for the accelerated loss of the T cells can be determined, perhaps the loss can be prevented. This would better equip patients to fight the infection.
Since 1998, a multi-pronged strategy of AIDS therapy has been established. Highly Active Anti-Retroviral Therapy (HAART) consists of administering a "cocktail" of drugs targeted to the AIDS virus to a patient, even when the patient shows no symptoms of AIDS. The drug mixture typically contains a so-called nucleoside analog, which blocks genetic replication, and inhibitors of two enzymes that are critical enzyme in the making of new virus (protease and reverse transcriptase).
HAART has greatly reduced the loss of life due to AIDS. But, this benefit has come at the expense of side effects that can often be severe. Also, the treatment is expensive. But now, research published toward the end of 2001 indicates that the use of HAART in a "7-day-on, 7-day-off" cycle does not diminish treatment benefits, but does diminish treatment side effects. Costs of treatment has become more reasonable, as well.
Another advancement in AIDS treatment may come from the finding that the inner core of the AIDS virus, which is called the nucleocapsid, is held together by structures known as "zinc fingers." There are drugs that appear to break apart these supports. This stops the virus from functioning. Furthermore, evidence supports the view that the nucleocapsid does not change much over time. Thus, a drug that effectively targeted the nucleocapsid could be an effective drug for a long time. The drawback to this approach at the present time is that other structures in the body utilize zinc fingers. So, an anti-AIDS zinc finger strategy will have to be made very specific.
In the mid 1980s, there was great optimism that a vaccine for the AIDS virus would be developed within two years. However, this optimism soon disappeared. In late 2001, however, preliminary clinical trials began on a candidate vaccine. Traditional vaccines rely on the administration of a protein to stimulate the production of an antibody that confers protection against the disease-causing organism. The candidate vaccine works by targeting what is called cell-mediated immunity. This type of immunity does not prevent infection, but rather clears the virus-infected cells out of the body. Such a vaccine would be intended to prolong and enhance the quality of the lives of AIDS-infected people. Studies in monkeys have been encouraging. However, studies must still rule out the possibility that vaccination would create "carriers," individuals who are not sick but who are capable of spreading the disease.
There are various vaccine treatment strategies. One involves the injection of so-called "naked" DNA. The DNA contains genes that code for gag, a viral component thought to be critical to the development of AIDS. The DNA can be attached to inert particles that stimulate the response of the immune system. In another strategy, the viral gene is bundled into the DNA of another virus that is injected into the patient.
As of 2002, more than two dozen experimental vaccines intended to control, but not cure, AIDS infections are being studied worldwide.
Treatment strategies, vaccine-based or otherwise, will need to address the different isolates of the AIDS virus that are present in various regions of the globe. These different isolates tend to be separated into different geographical regions. Even within a geographical area, an isolate can display variation from place to place. Thus, it has become clear that a universal treatment strategy is unlikely.
See also Human immunodeficiency virus (HIV); Immune stimulation, as a vaccine; Vaccination