12th World AIDS Conference
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...bridging the gap

LAST UPDATE: Wednesday, 1 July, 1998 19:08 GMT   S U M M A R Y     S E S S I O N S    ...all the news, as it happens

Summary of Tuesday, 30 June, 1998


One might say, more so than ever, that the basic science sessions at this year’s International AIDS Conference bring to the forefront the importance for intensification of research efforts in understanding the immune system and its role in both driving and controlling HIV replication.

Tuesday’s basic science sessions highlighted new developments in research on :

  • how the virus interacts with the immune system and;
  • how it can destroy the capacity of the infected individual to respond to HIV.

Another major topic was the reservoir of infected cells left in people who are receiving potent anti-HIV therapy. Emphasis was placed on CD4+ T cells that remain in the immune tissue (i.e. lymph nodes) and may hold the virus silent or leave it producing low levels of virus.

Tuesday presentations on how certain normal immune responses may have a major impact on HIV replication heralded the theme noted above - the immune system, its defects and normal responses as a consequence of infection, is a critical force in HIV disease progression. The following is a summary of major themes presented and further elucidated.

  • It has been well established that shortly after initial HIV infection, hours to days, the virus establishes itself in resting CD4+ T cells. One way that researchers can look at CD4+ cells is by examining the percentage which are resting compared to those which are active.

A resting T cell becomes activated when it needs to function, such as respond to an infection. When a CD4+ cell is activated, it becomes a target for HIV infection. The majority of cells that become infected are destroyed by the infection. Some percentage of cells, however, return to a quiet, resting state.

The infected resting T cell becomes a reservoir for HIV. Nearly all of the currently available anti-HIV drugs do not affect the virus unless it is in an active state. Moreover, when the virus is lying dormant in resting cells it is hidden from the immune system.

Thus, virus in these resting cells is capable of rekindling the fires of HIV infection and represents a threat to long-term and continued control of HIV with the currently available anti-HIV therapies.

  • A number of factors have been shown to increase HIV replication, cytokines, for example. Cytokines are naturally occurring immune chemicals that can be likened to the language of the immune system. Cells produce various cytokines as a means to communicate with one another, such as to initiate immune responses against infections.

    Certain cytokines, IL-1 beta, TNF-alpha and IL-6, have been shown to increase HIV replication. Studies have shown that therapy with a triple-drug protease inhibitor containing regimen decreases levels of some of these cytokines and also decreases HIV levels.

    Even in settings where HIV has been maximally suppressed, to below the limit of detection on sensitive tests, for long periods of time, there is typically a rebound in measurable virus when therapy is stopped.

    This virus is presumably coming from HIV infected resting cells that are driven by cytokines released from activated cells.

  • Another way that cytokines (e.g. IL-4) can affect HIV is by affecting co-receptor expression. In Monday’s summary, we discussed the role of CXCR4 and CCR5. One study showed that IL-4, in a test tube, increased CXCR4 on cells and reduced CCR5 on cells. This may lead to an increase in the HIV type (i.e. SI) which utilizes CXCR4 for cell entry, and these types of virus are more aggressive.
  • Given that current therapies cannot attack this reservoir for HIV infection, approaches that enhance the ability of the immune system to control HIV are critical. Another potential solution to this problem, however, may be to purge the reservoir, either by destroying the cells with immune ablative techniques, or by aggressively activating these quiet cells in order to make the virus in them visible to anti-HIV drugs as well as the immune response. Some of these approaches are currently being tested in studies.
  • One presentation highlighted information on the rate of viral decreases from a small number of people who received triple-drug therapy. The test used to measure HIV levels looked for virus inside of cells. The rate at which cell-associated virus decreased was highly variable between the patients.

    Despite HIV levels falling below the limit of detection of the currently available tests, cell-associated virus was detectable in all study participants.

    Discouraging was news that when examining the virus from volunteers at different time points, it was increasingly changing and mutating. This finding suggests that despite potent anti-HIV therapy, at some low level there is ongoing HIV replication.

    Fortunately, however, at least in those people studied, the mutating virus was not apparently developing resistance to the drugs. These findings were also observed in people recently infected by HIV who received anti-HIV therapy shortly after infection.

  • In addition to the direct infection and destruction of CD4+ T cells by HIV, other processes may be at work accounting for CD4+ T cell decline throughout the course of HIV disease.

Not only are CD4+ T cells being destroyed by HIV infection, but also there appears to be other processes, such as a defect in the production of new immune cells.

This defect may be at the level of the bone marrow, the environment from which all white blood cells are derived. HIV could interfere with a cell’s ability to go down its path of maturing. Also, HIV could infect the thymus, the key organ necessary for new T cell development.

Further exploration of these theories is important, and if correct could lead to new directions in research for HIV therapies.

Other notable new developments include :

  • Large numbers of groups have used DNA-based vaccine approaches in HIV uninfected people and in animals. Others have combined this approach with the use of vaccines employing the canarypox virus carrying an HIV protein.

The anti-HIV immune responses to these novel vaccine approaches have been noted, including antibody responses and in some cases cellular responses.

In one study cellular responses generated appeared to be effective against strains of viruses found in diverse parts of the world (i.e. across clades).

  • In Monday’s summary we discussed the role of chemokines and chemokine receptors in HIV infection. Studies presented on Tuesday indicated that chemokines can increase or decrease HIV replication depending on the amount of chemokine to which the cells are exposed.



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