12th World AIDS Conference
  
back to front page      All the news, as it happens  aids98.ch
back to today's front page

...bridging the gap

LAST UPDATE: Tuesday, 30 June, 1998 18:06 GMT   S U M M A R Y     S E S S I O N S  ...all the news, as it happens
T R A C K  A T R A C K  B T R A C K  C T R A C K  D COMMUNITY

BASIC SCIENCE - TRACK A
BASIC SCIENCE - TRACK A
Summary of Monday, 29 June, 1998

 
  • Monday’s basic science sessions of the 12th World AIDS Conference highlighted major information on immune recovery following the use of highly active anti-HIV therapy, which typically includes three drugs including a potent protease inhibitor. Additionally, new advances in understanding the virus’s interaction with cells shed light on new targets to inhibit HIV replication and possibly transmission.
  • In the course of HIV disease, many cell populations decrease over time. These include CD4+ cells, CD8+ cells (which initially increase and subsequently decrease throughout the course of disease), B cells and many other important immune system cells. In addition to a decrease in cell numbers, there are also profound defects in immune functions. CD8+ cells, which are important for directly destroying HIV infected cells and also produce factors which can inhibit HIV replication, do not appear to maintain anti-HIV activity, despite initial increases in CD8+ cell number. Moreover, the ability of the immune system to respond to a large number of infections becomes increasingly restricted. The environments necessary for new cell development and maturation (such as the bone marrow and thymus) might also be impaired as a consequence of HIV infection, making the prospect of immune restoration a challenge.
  • Presentations from the recent conference largely confirmed previous observations that treatment with aggressive anti-HIV therapy (e.g. triple-drug protease inhibitor containing regimens) appears to improve many immunologic abnormalities associated with HIV infection. Nevertheless, improvements are noted in almost every area including an increase in cell number and functional responses, these improvements are not the same as those observed in healthy, HIV-uninfected people, however. The following are highlights of new information presented at the conference on Monday:
  • Restoration of functional immune responses to common infections has been observed following anti-HIV therapy. Immune responses against HIV, however, appear to only be maintained in people treated very early (e.g. days to weeks following infection by HIV), but do not recover as a consequence of anti-HIV therapy in people treated at other stages of HIV disease.
  • People who initiate therapy at other stages of HIV disease demonstrate improvements in certain types of anti-HIV immune responses (e.g. HIV-specific CTL) if they are able to maintain suppression of virus for an extended period of time (e.g. greater than 2 years).
  • Exciting preliminary observations come from a group which imaged the thymus of HIV-infected children before and after anti-HIV therapy. In one representative case, the thymus before therapy was barely visible (0.07 cm3 in area). One year after starting therapy, the size of the thymus increased 100 fold (19.8 cm3 in area). This was a child who was quite advanced in disease with an AIDS diagnosis (CDC Class III). This increase was also associated with an increase in the proportion of na´ve T cells – perhaps new cells being generated from the thymus. This news is encouraging suggesting that this important immune environment, critical for new T cells with diverse abilities to mature, is able to function to some degree. More research is necessary in both adults and children to better understand this preliminary observation.
  • A large portion of Monday’s presentation highlighted new information on fairly recent and important discoveries on the role of cell proteins, called chemokine receptors, and immune chemicals, called chemokines, in the process of HIV infection of immune cells. Initially two proteins, CXCR4 and CCR5, were identified as critical co-receptors necessary for HIV to attach to in order to infect an immune cell. What that means is that in addition to the CD4+ protein on T-cells, HIV must also attach to a second protein in order to gain entry into a cell. CCR5 was identified as the second receptor important for the most commonly sexually transmitted strain of HIV (the NSI virus). CXCR4 was identified as the second protein important for enabling a more aggressive form of HIV (the SI virus) to infect a cell. This virus is more predominant among people in advanced-stage disease. Chemokines, natural products of many cells can bind to the second receptors, rendering the co-receptor inaccessible to the virus and thus inhibiting infection of immune cells. The conference highlighted the following advances in this important area of discovery:
  • Viruses from people who are long-term non-progressors (e.g. do not show symptoms of HIV disease progression after infection for 10+ years) appear to restrictively use the CCR5 protein in order to infect immune cells.
  • Viruses from people who follow a more traditional course of HIV disease progression will sometimes restrictively use CCR5, but not in all cases. This means that factors associated with disease progression and non-progression are not solely explained by the restricted use of certain co-receptors by the virus.
  • The majority of people who progress very rapidly to disease appear to have viruses which use many different co-receptors in order to infect immune cells.
  • This information, taken together, supports the need for further research on the role of co-receptor utilisation and disease progression in order to shed light on what processes are at work which conserves the use of certain receptors by the virus. Moreover, this information provides the basis for new directions in novel therapies for HIV disease.
  • A number of new therapeutic approaches, which interfere with HIV’s ability to access a co-receptor, are being evaluated in test tubes and animals. These include a class of drugs called biclyclams. AOP Rantes, a drug which resembles a chemokine, is also being researched.
  • While it is encouraging that new therapeutic approaches are being evaluated, there are concerns that inhibiting one pathway (e.g. CCR5) may drive the virus to start using another pathway (e.g. CXCR4), and may have detrimental effects on the disease.

Other notable new developments included:

  • Infected human immune cells were put in the vagina of a mouse (SCID-hu PBL) and productive infection was established in human white cells that had been put in the mouse. This model may be very useful for understanding transmission and testing HIV prevention approaches.
  • One showed that cells releasing HIV that is protease deficient can transmit virus that is infectious by cell-to-cell contact.
  • One point is clear from all presentations at this conference - better tools to measure immune system are critical in order to fully understand immune restoration as a product of therapy, as well as to garner a better understanding of HIV disease.

    help!want more?
    additional news is available
    on today's front page

Back to Today's Front Page back